Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero...Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.展开更多
Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit...Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.展开更多
Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoprotein...Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.展开更多
Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially whe...Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.展开更多
Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,bec...Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.展开更多
Dietary omega-3 polyunsaturated fatty acids(ω-3 PUFAs)can be classifi ed into animal-and plant-derivedω-3 PUFAs.Patients with type 2 diabetes(T2DM)are frequently accompanied by dyslipidemia,which is closely related ...Dietary omega-3 polyunsaturated fatty acids(ω-3 PUFAs)can be classifi ed into animal-and plant-derivedω-3 PUFAs.Patients with type 2 diabetes(T2DM)are frequently accompanied by dyslipidemia,which is closely related to the high-density lipoprotein(HDL-C)subfractions change.This study aimed to determine the effects of different sourcesω-3 PUFAs on glucolipid metabolism and lipoprotein subfractions in T2DM with dyslipidemia.Ninety T2DM patients with dyslipidemia were randomly assigned to take 3 g/day fi sh oil(FO,containing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)),3 g/day perilla oil(PO,containingα-linolenic acid(ALA)),or 3 g/day blend oil(BO,containing EPA,DHA and ALA)for 3 months.90 patients completed the intervention.There was a significant reduction of glycated hemoglobin(HbA1c)in all the groups.The triglycerides(TG)in the FO group were signifi cantly different with a group×time interaction(P=0.043),which was higher compared with the other two groups.The serum small HDL-C subfractions in the PO group was higher and the serum large HDL-C subfractions in the PO group was lower than those in the BO and FO groups.Plant-derivedω-3 PUFAs are more effective at controlling blood glucose than animal-derivedω-3 PUFAs.However,animal-derivedω-3 PUFAs have a signifi cant lowering effect on TG compared with plant-derivedω-3 PUFAs.Particularly,large HDL-C subfractions after animal-derivedω-3 PUFAs intake were higher than plant-derivedω-3 PUFAs intake;while small HDL-C subfractions were lower.Both the animal-and plant-derivedω-3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.展开更多
BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which ...BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.展开更多
Patients living with chronic kidney disease (CKD) are at high risk of cardiovascular events. Our aim in this study was to assess the cut-off value for lipoprotein (a) (Lp(a)) in CKD patients with a history of cardiova...Patients living with chronic kidney disease (CKD) are at high risk of cardiovascular events. Our aim in this study was to assess the cut-off value for lipoprotein (a) (Lp(a)) in CKD patients with a history of cardiovascular disease (CVD). This was a cross-sectional study. Variables including age, sex, history of CVD, body mass index and CKD stage, were collected during CKD patient’s first admission in the nephrology dialysis department. Blood samples were collected for quantitative determination of Lp(a) by immunoturbidimetric method. They were divided into two groups: CKD patients without history of CVD and CKD patients with history of CVD. Fisher’s exact test was used to assess associations with a significance level of 0.05%. Area under the curve (AUC) and new cut-off value for Lp(a) were identified by drawing Receiver Operating Characteristic (ROC) curve. A total of seventy CKD patients with median age of 43 years [minimum-maximum = 15 - 78 years] were included. Patients with history of CVD were 65.71% (46/70). New Lp(a) cut-off point in CKD patients with history of CVD was 66.50 nmol/L [sensitivity, 87.00%;specificity, 58.30%;AUC = 0.727;p = 0.000]. ROC curve demonstrated good performance of Lp(a) to screen CKD patients with history of CVD. Further research is needed to determine an LPA gene polymorphism’s contribution to increasing risk for CVD at each kidney disease stage.展开更多
Aim: To evaluate the impact of age and gender on lipid and lipoprotein profiles and the burden of dyslipidemia in a cohort of healthy Chinese Singaporean. Methods: A total of 1 775 healthy Chinese, 536 men and 1 239...Aim: To evaluate the impact of age and gender on lipid and lipoprotein profiles and the burden of dyslipidemia in a cohort of healthy Chinese Singaporean. Methods: A total of 1 775 healthy Chinese, 536 men and 1 239 women aged between 30 and 70 years old were involved in the present study. Results: Gender differences in all lipid and lipoprotein levels were clearly evident. Singaporean Chinese men have significantly higher levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and total cholesterol/high density lipoprotein-cholesterol (TC/HDL-C), and lower levels of HDL-C than women. Although lipid and lipoprotein levels in men did not change in the different age groups, those in women, especially TC, LDL-C and TC/HDL-C, were significantly higher in older women (〉 50 years old) than corresponding levels in younger women (30-46 years old). Furthermore, TG was significantly correlated with lipids and lipoproteins differently in men and women. If 100 mg/dL of LDL-C were to be adopted as the therapeutic cut-off level, then the burden of care will be huge as approximately 90% of both Chinese men and women have LDL-C greater than 100 mg/dL. Condusion: In light of the findings of the present study, we suggest that preventive measures to promote the reduction in risk of coronary heart disease (CHD) must address the high proportion of men and women with high LDL-C, and that these measures should take into account both the gender and age factors. For men, reduction of high cholesterol must start early in life, whereas for women, steps must be taken earlier to mitigate the anticipated sharp increase in risk, especially after menopause.展开更多
Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered ...Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered as the best predictor of CVD. Thus this study was carried out to find out the association between conventional lipid parameters and apoB in apparently healthy subjects. A descriptive cross-sectional study was carried out in 170 apparently healthy volunteers who were not diagnosed with dyslipidaemia. After 12 hours overnight fast venous blood was obtained and Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL-C) were measured by enzymatic kit method. Low density lipoprotein cholesterol (LDL-C) was calculated by Friedewald formula and apoB was analyzed by immune turbid metry using a Konelab<sup>®</sup> auto analyzer. Among the participants, majority (63.5%) were females. The mean value of apoB concentration of the population was 103 ± 42 mg/dL which was similar and not significantly different between the genders (Males, 102 ± 37 mg/dL and Females, 104 ± 45 mg/dL). All lipid parameters showed a positive correlation with apoB concentration whereas HDL-C had a negative correlation (r = -0.165). HDL-C significantly (p < 0.05) decreased with increase in apoB concentration while LDL-C, TC/HDL-C and non-HDL-C significantly (p < 0.05) increased with an increase in apoB concentration. Present study suggests that serum apoB has better correlations and associations with the parameters that are used in conventional lipid profile and with markers recommended for diagnosing dyslipidaemia. Hence apoB could be used as a single marker for screening dyslipidaemia in apparently healthy people.展开更多
Nonalcoholic fatty liver disease (NAFLD), an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to li...Nonalcoholic fatty liver disease (NAFLD), an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.展开更多
Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence a...Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.展开更多
It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been det...It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.展开更多
Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other...Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other physiological functions such as immune regulation.In particular,neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids.For this reason,the role of certain lipoproteins and their protein-component(apolipoproteins,Apo’s)in neurological diseases is perceivable.ApoE,for example,is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant(ε2)and a risk-causing allele variant(ε4).ApoA1,the major protein component of high-density lipoproteins,is responsible for transportation of excess cholesterol from peripheral tissues to the liver.The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis.This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.展开更多
Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the ...Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.展开更多
BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other S...BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid profiles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords 'hepatocellular carcinoma' and 'lipoprotein(a)'. The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apolipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolism in vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein (a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display significant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.展开更多
AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV...AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1 b infection(active HCV group) and 91 with cleared HCV infection(SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using Lipo SEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1 b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein(LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range(IQR): 444 nmol/L] than in the SVR group(1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of highdensity lipoprotein(HDL) particles(14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein(VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium(median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small(median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles(median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1 b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1 b infection decreases the numbers of medium, small, and very small LDL particles.展开更多
Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TC...Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.展开更多
Apolipoprotein A-Ⅱ(APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein(HDL)synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing huma...Apolipoprotein A-Ⅱ(APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein(HDL)synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis, though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial. Here, we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity. C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus Ad GFP, and five days post-infection blood and tissue samples were isolated. APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities. No effects on cholesterol efflux from RAW 264.7 macrophages were observed. Molecular analyses in white adipose tissue(WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ. Finally, overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin. In summary, expression of APOA-Ⅱ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality, adipose tissue metabolism and glucose utilization, many of which are beneficial to health.展开更多
Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease (CVD). The highly dynamic lipoprotein molecules are capable of...Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease (CVD). The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein (HDL) and low-density lipoprotein (LDL) are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein (HDL and LDL) elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.展开更多
基金supported by the National Key R&D Program of China (2022YFE0196200)the National Natural Science Foundation of China–Deutsche Forschungsgemeinschaft of Germany (31761133021)+3 种基金the National Natural Science Foundation of China (31970469 and 31701794)the earmarked fund for Modern Agro-industry Technology Research System, China (2023CYJSTX01-20)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China (2017104)the Fund for Shanxi “1331 Project”, China
文摘Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.
基金supported by the National Natural Science Foundation of China,No.82201460(to YH)Nanjing Medical University Science and Technology Development Fund,No.NMUB20210202(to YH).
文摘Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
文摘Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.
基金the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNLH-201907)the Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019Q041)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(No.2021-I2M-1-009).
文摘Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.
基金financial support from the National Natural Science Foundation of China(No.82274104,82074024,82374042)the Open Project of Chinese Materia Medica FirstClass Discipline of Nanjing University of Chinese Medicine(No.2020YLXK019)Young Elite Scientists Sponsorship Program by CACM(No.2021-QNRC2-A01)
文摘Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.
基金supported by the two National Natural Science Foundations of China(81872618 and 81573144).
文摘Dietary omega-3 polyunsaturated fatty acids(ω-3 PUFAs)can be classifi ed into animal-and plant-derivedω-3 PUFAs.Patients with type 2 diabetes(T2DM)are frequently accompanied by dyslipidemia,which is closely related to the high-density lipoprotein(HDL-C)subfractions change.This study aimed to determine the effects of different sourcesω-3 PUFAs on glucolipid metabolism and lipoprotein subfractions in T2DM with dyslipidemia.Ninety T2DM patients with dyslipidemia were randomly assigned to take 3 g/day fi sh oil(FO,containing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)),3 g/day perilla oil(PO,containingα-linolenic acid(ALA)),or 3 g/day blend oil(BO,containing EPA,DHA and ALA)for 3 months.90 patients completed the intervention.There was a significant reduction of glycated hemoglobin(HbA1c)in all the groups.The triglycerides(TG)in the FO group were signifi cantly different with a group×time interaction(P=0.043),which was higher compared with the other two groups.The serum small HDL-C subfractions in the PO group was higher and the serum large HDL-C subfractions in the PO group was lower than those in the BO and FO groups.Plant-derivedω-3 PUFAs are more effective at controlling blood glucose than animal-derivedω-3 PUFAs.However,animal-derivedω-3 PUFAs have a signifi cant lowering effect on TG compared with plant-derivedω-3 PUFAs.Particularly,large HDL-C subfractions after animal-derivedω-3 PUFAs intake were higher than plant-derivedω-3 PUFAs intake;while small HDL-C subfractions were lower.Both the animal-and plant-derivedω-3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.
基金The study was reviewed and approved by the Institutional Review Board of Chaohu Hospital Affiliated to AnhuiMedical University,Approval No.KYXM-202208-011.
文摘BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.
文摘Patients living with chronic kidney disease (CKD) are at high risk of cardiovascular events. Our aim in this study was to assess the cut-off value for lipoprotein (a) (Lp(a)) in CKD patients with a history of cardiovascular disease (CVD). This was a cross-sectional study. Variables including age, sex, history of CVD, body mass index and CKD stage, were collected during CKD patient’s first admission in the nephrology dialysis department. Blood samples were collected for quantitative determination of Lp(a) by immunoturbidimetric method. They were divided into two groups: CKD patients without history of CVD and CKD patients with history of CVD. Fisher’s exact test was used to assess associations with a significance level of 0.05%. Area under the curve (AUC) and new cut-off value for Lp(a) were identified by drawing Receiver Operating Characteristic (ROC) curve. A total of seventy CKD patients with median age of 43 years [minimum-maximum = 15 - 78 years] were included. Patients with history of CVD were 65.71% (46/70). New Lp(a) cut-off point in CKD patients with history of CVD was 66.50 nmol/L [sensitivity, 87.00%;specificity, 58.30%;AUC = 0.727;p = 0.000]. ROC curve demonstrated good performance of Lp(a) to screen CKD patients with history of CVD. Further research is needed to determine an LPA gene polymorphism’s contribution to increasing risk for CVD at each kidney disease stage.
文摘Aim: To evaluate the impact of age and gender on lipid and lipoprotein profiles and the burden of dyslipidemia in a cohort of healthy Chinese Singaporean. Methods: A total of 1 775 healthy Chinese, 536 men and 1 239 women aged between 30 and 70 years old were involved in the present study. Results: Gender differences in all lipid and lipoprotein levels were clearly evident. Singaporean Chinese men have significantly higher levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and total cholesterol/high density lipoprotein-cholesterol (TC/HDL-C), and lower levels of HDL-C than women. Although lipid and lipoprotein levels in men did not change in the different age groups, those in women, especially TC, LDL-C and TC/HDL-C, were significantly higher in older women (〉 50 years old) than corresponding levels in younger women (30-46 years old). Furthermore, TG was significantly correlated with lipids and lipoproteins differently in men and women. If 100 mg/dL of LDL-C were to be adopted as the therapeutic cut-off level, then the burden of care will be huge as approximately 90% of both Chinese men and women have LDL-C greater than 100 mg/dL. Condusion: In light of the findings of the present study, we suggest that preventive measures to promote the reduction in risk of coronary heart disease (CHD) must address the high proportion of men and women with high LDL-C, and that these measures should take into account both the gender and age factors. For men, reduction of high cholesterol must start early in life, whereas for women, steps must be taken earlier to mitigate the anticipated sharp increase in risk, especially after menopause.
文摘Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered as the best predictor of CVD. Thus this study was carried out to find out the association between conventional lipid parameters and apoB in apparently healthy subjects. A descriptive cross-sectional study was carried out in 170 apparently healthy volunteers who were not diagnosed with dyslipidaemia. After 12 hours overnight fast venous blood was obtained and Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL-C) were measured by enzymatic kit method. Low density lipoprotein cholesterol (LDL-C) was calculated by Friedewald formula and apoB was analyzed by immune turbid metry using a Konelab<sup>®</sup> auto analyzer. Among the participants, majority (63.5%) were females. The mean value of apoB concentration of the population was 103 ± 42 mg/dL which was similar and not significantly different between the genders (Males, 102 ± 37 mg/dL and Females, 104 ± 45 mg/dL). All lipid parameters showed a positive correlation with apoB concentration whereas HDL-C had a negative correlation (r = -0.165). HDL-C significantly (p < 0.05) decreased with increase in apoB concentration while LDL-C, TC/HDL-C and non-HDL-C significantly (p < 0.05) increased with an increase in apoB concentration. Present study suggests that serum apoB has better correlations and associations with the parameters that are used in conventional lipid profile and with markers recommended for diagnosing dyslipidaemia. Hence apoB could be used as a single marker for screening dyslipidaemia in apparently healthy people.
文摘Nonalcoholic fatty liver disease (NAFLD), an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.
基金Supported by AIRC(to Tripodi MNo.IG-13529 to Fimia GM)+6 种基金Ministry for Health of Italy(“Ricerca Corrente”to Grassi GTripodi MAlonzi TFimia GM and Ippolito G“Ricerca Finalizzata”to Fimia GM and Ippolito G)Ministry of University and Research of Italy(PRIN to Tripodi MPh D program to Di Caprio G)
文摘Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.
基金This work was supported,in part,by Capital Special Foundation of Clinical Application Research(No.Z121107001012015)Capital Health Development Fund(No.201614035)+1 种基金CAMS Major Collaborative Innovation Project(No.2016-I2M-1-011)PUMC Youth Fund(No.3332018200).
文摘It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.
基金supported by grants from the MWWK,Germany(research consortium NeuroDegX)to KE.
文摘Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other physiological functions such as immune regulation.In particular,neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids.For this reason,the role of certain lipoproteins and their protein-component(apolipoproteins,Apo’s)in neurological diseases is perceivable.ApoE,for example,is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant(ε2)and a risk-causing allele variant(ε4).ApoA1,the major protein component of high-density lipoproteins,is responsible for transportation of excess cholesterol from peripheral tissues to the liver.The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis.This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.
文摘Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.
文摘BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid profiles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords 'hepatocellular carcinoma' and 'lipoprotein(a)'. The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apolipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolism in vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein (a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display significant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.
文摘AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1 b infection(active HCV group) and 91 with cleared HCV infection(SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using Lipo SEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1 b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein(LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range(IQR): 444 nmol/L] than in the SVR group(1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of highdensity lipoprotein(HDL) particles(14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein(VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium(median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small(median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles(median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1 b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1 b infection decreases the numbers of medium, small, and very small LDL particles.
文摘Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.
基金supported financially by the program"Support of Young Investigators"MIS No.5005458 that was co-financed by the Operational Program"Human Resources Development,Education and Lifelong Learning"and by the European Union(European Social Fund)and Greek national funds。
文摘Apolipoprotein A-Ⅱ(APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein(HDL)synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis, though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial. Here, we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity. C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus Ad GFP, and five days post-infection blood and tissue samples were isolated. APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities. No effects on cholesterol efflux from RAW 264.7 macrophages were observed. Molecular analyses in white adipose tissue(WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ. Finally, overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin. In summary, expression of APOA-Ⅱ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality, adipose tissue metabolism and glucose utilization, many of which are beneficial to health.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11504287 and 11774279)
文摘Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease (CVD). The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein (HDL) and low-density lipoprotein (LDL) are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein (HDL and LDL) elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.