Diagnostic and prognostic implications of non-high-density lipoprotein cholesterol and homocysteine levels for cognitive impairment in thalamic infarction

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.

Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.METHODS We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects.The levels of serum total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS.Then,we used the data from Oncomine to screen the differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs.PrognoScan was used to analyze the prognostic value of the DEGs,and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs.RESULTS The serum HDL-C level in CRC patients was significantly correlated with tumor size,and patients whose tumor size was more than 5 cm had a lower serum HDL-C level(1.18±0.41 mmol/L vs 1.25±0.35 mmol/L,P<0.01)than their counterparts.In addition,TC/HDL(4.19±1.33 vs 3.93±1.26,P<0.01)and LDL-C/HDL-C(2.83±1.10 vs 2.61±0.96,P<0.01)were higher in patients with larger tumors.The levels of HDL-C(P<0.05),TC/HDL-C(P<0.01)and LDL-C/HDL-C(P<0.05)varied in different stages of CRC patients,and the differences were significant.We screened 14 differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8(LRP8),PCSK9,low-density lipoprotein receptor(LDLR),MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in cancer tissue.Higher expression of LDLR(HR=3.12,95%CI:1.77-5.49,P<0.001),ABCA1(HR=1.66,95%CI:1.11-2.48,P=0.012)and OSBPL1A(HR=1.38,95%CI:1.01-1.89,P=0.041)all yielded significantly poorer DFS outcomes.Higher expression of FDXR(HR=0.7,95%CI:0.47-1.05,P=0.002)was correlated with longer DFS.LDLR,ABCA1,OSBPL1A and FDXR were involved in many important cellular function pathways.CONCLUSION Serum HDL-C levels are associated with tumor size and stage in CRC patients.LRP8,PCSK9,LDLR,MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in CRC.Among them,LDLR,ABCA1,OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.

Comparison of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol for the prediction of thin-cap fibroatheroma determined by intravascular optical coherence tomography

Background The correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol(LDL-C/HDL-C), total cholesterol/high-density lipoprotein cholesterol(TC/HDL-C) and thin-cap fibroatheroma has not yet been established. Methods It was a single center, retrospective observational study. In total, we recruited 421 patients(82.4% men;mean age 65.73 ± 10.44 years) with one culprit vessel which determined by intravascular optical coherence tomography(OCT). The thinnest-capped fibroatheroma(TCFA) group was defined as lipid contents in > 2 quadrants, with the thinnest fibrous cap measuring less than 65 μm. Univariate and multivariate logistic regression were carried out to explore the relationship between lipoprotein ratios, TCFA and other characteristics of plaque. To compare different ratios, the area under curve(AUC) of receiver-operating characteristic(ROC) curve was assessed. Results OCT was performed in 421 patients(TCFA group(n = 109), non-TCFA group(n = 312)). LDL-C/HDL-C in the TCFA group was significantly higher than in the non-TCFA group(2.95 ± 1.20 vs. 2.43 ± 0.92, P < 0.05), as was TC/LDL in TCFA and non-TCFA group(4.57 ± 1.58 vs. 4.04 ± 1.13, P < 0.05). Both LDL-C/HDL-C(OR: 1.002(1.002-1.003), P < 0.05) and TC/HDL-C(OR: 1.001(1.001-1.004), P < 0.05) were considered independent factors for the prediction of TCFA according to the logistic regression. Based on the AUC comparison, LDL-C/HDL-C and TC/HDL-C had no significant difference statistically(LDL-C/HDL-C AUC: 0.63;TC/HDL-C AUC: 0.61;P = 0.10) for the prediction of TCFA. Conclusions LDL-C/HDL-C and TC/HDL-C could be the independent factors for predicting the presence of TCFA, indicating coronary plaque vulnerability in CAD patients. Moreover, TC/HDL-C also showed a comparative performance for the prediction of TCFA as LDL-C/HDL-C.

High-density Lipoprotein Cholesterol and In-hospital Mortality in Patients with Acute Aortic Dissection

The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.

Total cholesterol to high-density lipoprotein ratio and nonalcoholic fatty liver disease in a population with chronic hepatitis B

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is characterized by hypertriglyceridemia,increased low-density lipoprotein cholesterol levels,and reduced highdensity lipoprotein cholesterol(HDL-C)particles.Previous studies have shown that the total cholesterol to high-density lipoprotein cholesterol ratio(TC/HDL-C)was superior to other lipid metabolism biomarkers for predicting NAFLD risk and could be a new indicator of NAFLD.However,the association between TC/HDL-C and NAFLD in patients with hepatitis B virus(HBV)has not yet been determined.AIM To investigate the association between TC/HDL-C and NAFLD in a population with chronic hepatitis B(CHB).METHODS In this study,183 HBV-infected patients were enrolled.All participants underwent blood chemistry examinations and abdominal ultrasound.Univariate and multivariate logistic regression models,curve fitting analysis,and threshold calculation were used to assess the relationship between TC/HDL-C and NAFLD.RESULTS The overall prevalence of NAFLD was 17.49%(n=32)in the 183 CHB participants.The TC/HDL-C of non-NAFLD and NAFLD patients were 3.83±0.75 and 4.44±0.77,respectively(P<0.01).Logistic regression analysis showed that TC/HDL-C was not associated with NAFLD after adjusting for other pertinent clinical variables.However,at an optimal cutoff point of 4.9,a non-linear correlation between TC/HDL-C and NAFLD was detected.The effect size of the left and right sides of the inflection point were 5.4(95%confidence interval:2.3-12.6,P<0.01)and 0.5(95%confidence interval:0.1-2.2,P=0.39),respectively.On the left side of the inflection point,TC/HDL-C was positively associated with NAFLD.However,no significant association was observed on the right side of the inflection point.CONCLUSION This study demonstrated a non-linear correlation between TC/HDL-C and NAFLD in a population with CHB.TC/HDL-C was positively associated with NAFLD when TC/HDL-C was less than 4.9 but not when TC/HDL-C was more than 4.9.

Serum non-high-density lipoprotein cholesterol level is increased in Chinese patients with nonalcoholic fatty liver disease

To the Editor:Nonalcoholic fatty liver disease(NAFLD)is a growing public health problem globally.Although the primary liver pathology in NAFLD patients is associated with an increased risk of overall mortality,the majority of deaths in NAFLD patients are due to the cardiovascular disease(CVD)[1].With the change of lifestyle,the prevalence of NAFLD in China is increasing and patients tend to be younger[2].A relevant epidemiological survey has shown that the prevalence of NAFLD in adults is estimated to be 12%–24%in Asia[3].Non-high-density lipoprotein cholesterol(non-HDL-C)refers to the sum of all cholesterol subtracts high-density lipoprotein cholesterol(HDL-C),which can more comprehensively reflect the comprehensive metabolic changes of lipoproteins including low-density lipoprotein cholesterol(LDL-C),intermediate-density lipoprotein cholesterol(IDL-C),and very-low-density lipoprotein cholesterol(VLDL-C)[4].Recently,NAFLD that often coexists with dyslipidemia has been identified as a major modifiable risk factor of CVD,and non-HDL-C has become a new biomarker for assessing and predicting the risk of CVD[4].

Prevalence of High Non-high-density Lipoprotein Cholesterol and Associated Risk Factors in Patients with Diabetes Mellitus in Jilin Province,China:A Cross-sectional Study

Dyslipidemia is a risk factor for cardiovascular diseases（CVDs）in patients with diabetes,and non-high-density lipoprotein cholesterol（non-HDL-C）is a better predictor of CVDs than low-density lipoprotein cholesterol（LDL-C）in patients with diabetes.Therefore,we aimed to investigate the distribution of non-HDL-C and the prevalence of high non-HDL-C level in Chinese patients with diabetes mellitus and identify the

A Possible Mechanism Linking Hyperglycemia and Reduced High-density Lipoprotein Cholesterol Levels in Diabetes

This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24,48 and 72 h after glucose treatment.The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points(P>0.05 for each).In the 30 mmol/L glucose group,macrophage ABCA1 mRNA expression was not changed significantly at 24 h(P=0.14),but was substantially decreased by 40.4% at 48 h(P=0.009) and by 48.1% at 72 h(P=0.015) as compared with that in the control group.It was concluded that ABCA1 is of vital importance for HDL-C biogenesis.High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression,which contributes to low HDL-C level in diabetes.

Relationship of Circulating High-Density Lipoprotein Cholesterol and Anemia

Circulating level of low HDLC （high-density lipoprotein cholesterol） represents a common critical risk factor for IHD （ischemic heart disease） and may further aggravate the condition in anemic subjects, as the presence of anemia itself is a threat to cardiovascular consequences. To investigate the relationship of circulating HDLC with anemia, first we determined the levels of total hemoglobin （Hb） in a total of 301 subjects （male, n = 158; female, n = 143） randomly, and then examined the circulating levels of HDLC in fasting condition. Age of the study subjects was 47.9 ~ 16.6 （mean ＋ SD） years. Both the male and female subjects were divided into three groups according to their levels of Hb. The relationship of circulating levels of HDLC with the levels of total Hb was statistically analyzed. In case of the male subjects, we found that the levels of HDLC differed significantly among the three groups with different levels of Hb （P = 0.0233） and decrease in the levels of HDLC correlated significantly with the gradual decrease of total Hb level （r = 0.2504; P = 0.0015）. In female subjects, we observed a similar trend of difference among the three groups （P = 0.0685）. However, decrease in the levels of HDLC correlated significantly with the gradual decrease of Hb level （r = 0,2199; P = 0.0083）. Altogether, this study demonstrates that decrease in the circulating HDLC is related to the gradual decrease of Hb level. This study also indicates that circulating level of HDLC may be influenced by the level of total Hb and reveals the cardiovascular risks in anemia as well.

High-density lipoprotein and atherosclerosis: Roles of lipid transporters

Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells

AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells. METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method. RESULTS: The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 ug/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL.Cytotoxicity of the rHDL-ACM to SMMC- 7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells. CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes, HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.

The role of low-density lipoprotein （LDL） and high-density lipoprotein （HDL） in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

Low-density lipoprotein （LDL） extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein （HDL） in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant （glycerol） on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in pest-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

Effect of low high-density lipoprotein levels on mortality of septic patients: A systematic review and meta-analysis of cohort studies

BACKGROUND:An increase in high-density lipoprotein(HDL)is well associated with a decreased cardiovascular risk,especially atherosclerosis.Recent studies suggest that lower levels of HDL may also be associated with an increased risk of sepsis and an increased rate of mortality in septic patients.However,this conclusion remains controversial.METHODS:MEDLINE,EMBASE,and CENTRAL databases were searched from inception to September 30,2019.All studies were conducted to evaluate the correlation of lipoprotein levels and the risk and outcomes of sepsis in adult patients.The primary outcomes were the risk and mortality of sepsis.RESULTS:Seven studies comprising 791 patients were included.Lower levels of HDL had no marked relevance with the risk of sepsis(odds radio[OR]for each 1 mg/dL increase,0.94;95%CI 0.86–1.02;P=0.078),whereas lower HDL levels were related to an increased mortality rate in septic patients(OR for below about median HDL levels,2.00;95%CI 1.23–3.24;P=0.005).CONCLUSION:This meta-analysis did not reveal a signifi cant association between lower HDL levels and an increase in the risk of sepsis,whereas it showed that lower HDL levels are associated with a higher mortality rate in septic adult patients.These findings suggest that HDL may be considered as a promising factor for the prevention and treatment of sepsis in the future.

High-density lipoproteins:an emerging target in the prevention of cardiovascular disease

High-density lipoproteins （HDLs） have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.

Proso Millet Protein Elevates Plasma Level of High-Density Lipoprotein:A New Food Function of Proso Millet

We examined the effects of dietary proso-millet protein on plasma levels of high-density lipoprotein (HDL) cholesterol in different rats from animals reported in our previous studies. The results showed also, in this animal, that the ingestion of the millet protein elevates plasma levels of HDL-cholesterol like our earlier works. Taking into account the anti-atherogenic function of HDL, therefore, the millet protein would be useful as a new food ingredient which has the function that regulates cholesterol metabolism

Bone and high-density lipoprotein:The beginning of a beautiful friendship

There is a tight link between bone and lipid metabolic pathways.In this vein,several studies focused on the exploration of high-density lipoprotein(HDL)in the pathobiology of bone diseases,with emphasis to the osteoarthritis(OA)and osteoporosis,the most common bone pathologies.Indeed,epidemiological and in vitro data have connected reduced HDL levels or dysfunctional HDL with cartilage destruction and OA development.Recent studies uncovered functional links between HDL and OA fueling the interesting hypothesis that OA could be a chronic element of the metabolic syndrome.Other studies have linked HDL to bone mineral density.Even though at epidemiological levels the results are conflicting,studies in animals as well as in vitro experiments have shown that HDL facilitates osteoblastogensis and bone synthesis and most probably affects osteoclastogenesis and osteoclast bone resorption.Notably,reduced HDL levels result in increased bone marrow adiposity affecting bone cells function.Unveiling the mechanisms that connect HDL and bone/cartilage homeostasis may contribute to the design of novel therapeutic agents for the improvement of bone and cartilage quality and thus for the treatment of related pathological conditions.

Glycation of high-density lipoprotein triggers oxidative stress and promotes the proliferation and migration of vascular smooth muscle cells

Background In type 2 diabetes mellitus （T2DM）, high-density lipoprotein （HDL） impairs its anti-atherogenic properties and even develops to a pro-inflammatory and pro-atherogenic phenotype because of abnormal compositions and modifications. In this study, we ex- amined the effects and the related mechanisms of glycation of HDL on the proliferation and migration of vascular smooth muscle cells （VSMCs）. Methods ＆ Results Glycated HDL （G-HDL） was modified with D-glucose （25 mmol/L） in vitro. Diabetic HDL （D-HDL） was isolated from T2DM patients. Rat VSMCs were isolated from the thoracic aortas. Human VSMCs were obtained from ScienCell Research Laboratories. Alpha-actin was detected through immunofiuorescence. VSMC proliferation was assayed by Cell Count. VSMC migration was determined by transwell chamber and scratch-wound assay. Intracellular reactive oxygen species （ROS） was detected based on ROS-medi- ated 2＇,7＇-dichlorofluorescein （DCFH-DA） fluorescence. Compared to native HDL （N-HDL）, G-HDL remarkably promoted VSMC prolif- eration and migration in the dose and time-dependent manners. In addition, G-HDL enhanced ROS generation in VSMCs. However, the ROS scavenger, N-acetylcysteine, efficiently decreased ROS production and subsequently inhibited the proliferation of VSMCs induced by G-HDL. Similarly, D-HDL from T2DM patients also promoted ROS release and VSMC proliferation and migration. Conclusions HDL either glycated in vitro or isolated from T2DM patients triggered VSMC proliferation, migration, and oxidative stress. These results might partly interpret the higher morbidity of cardiovascular disease in T2DM patients.

Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein

The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.

Pleiotropic effects of apolipoprotein A-Ⅱ on high-density lipoprotein functionality, adipose tissue metabolic activity and plasma glucose homeostasis

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.

OXIDIZED HIGH-DENSITY LIPOPROTEIN PROMOTES MATURATION AND MIGRATION OF BONE MARROW DERIVED DENDRITIC CELLS FROM C57BL/6J MICE

Objective To explore the influence of oxidized high-density lipoprotein （oxHDL） on the maturation and migration of bone marrow-derived dendritic cells （BMDCs） from C57BL/6J mice. Methods The C57BL/6J mice bone marrow cell suspension was prepared and purified. Recombinant granulocyte-macrophage colony-stimulating factor （rmGM-CSF） and recombinant interleukin-4 （rmlL-4） were used to promote monocytes to differentiate and suppress lymphocytes. Then 50μg/mL oxHDL was added to stimulate BMDCs, using 50μg/mL high-density lipoprotein （HDL） as homologous protein control, PBS as negative control, and 1 μg/mL lipopolysaccharide （LPS） as positive control. The CD86 and MHCII expression rates were detected with fluorescence-activated cell sorting （FACS）. Liquid scintillation counting （LSC） was used in mixed lymphocyte reactions （MLRs） to reflect the ability of BMDCs in stimulating the proliferation of homologous T cells, Levels of cytokines IL-12 and IL-10 were detected by ELISA. The cell migration was evaluated with the transwell system. Results Compared with PBS group, the expressions of CD86 and MHCII, counts per minute of MLRs, secretion of IL-12 and IL-10, and number of migrated cells in oxHDL group and LPS group significantly increased （all P 〈 0.05）, while the increment was less in oxHDL group than LPS group. The number of migrated cells in oxHDL group was about twice of that in HDL group. Conclusion OxHDL may promote the maturation and migration of BMDCs in vitro.