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 studie...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.展开更多
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-...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.展开更多
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(D...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.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
Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipop...Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.展开更多
BACKGROUND At present,the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited.AIM To evaluate the value of a novel parameter for colorectal cancer(CRC)prognosis scori...BACKGROUND At present,the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited.AIM To evaluate the value of a novel parameter for colorectal cancer(CRC)prognosis scoring based on preoperative serum lipid levels.METHODS Four key serum lipid factors,namely,high-density lipoprotein cholesterol(HDLC),low-density lipoprotein cholesterol(LDL-C),apolipoprotein A1(Apo A1),and apolipoprotein B(Apo B),were detected.Two representative ratios,HDL-C-LDLC ratio(HLR)and Apo A1-Apo B ratio(ABR)were calculated.The relationship of these parameters with the prognosis of CRC patients including progression-free survival(PFS)and overall survival(OS)was analyzed by Kaplan-Meier plot and Cox proportional hazards regression.A novel lipoprotein cholesterol-apolipoprotein(LA)score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored.RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C,Apo A1,HLR,and ABR were positively associated with the prognosis of CRC patients.LA score was independently associated with a good prognosis in resectable CRC patients.Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores.CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.展开更多
、Background:Using health coaching to improve the quality of life and health outcomes of the patients with diabetes mellitus,has emerged as a possible intervention.However,the few published randomized controlled trial...、Background:Using health coaching to improve the quality of life and health outcomes of the patients with diabetes mellitus,has emerged as a possible intervention.However,the few published randomized controlled trials using health coaching for patients with diabetes mellitus have reported mixed results.The present meta-analysis aimed to determine the effectiveness of health coaching on modifying health status and quality of life among diabetic patients and to clarify the characteristics of coaching delivery that make it most effective.Methods:This study searched for articles on randomized controlled trials of health coaching interventions targeting type 2 diabetic patients that were published in the English language from January 2005 through December 2018 in the Cochrane,Medline,PubMed,Trip,and Embase databases.Patients in the control group received usual diabetes mellitus care,and those in the experimental group received health coaching based on usual diabetes mellitus care.The primary outcomes included Hemoglobin A1c(HbA1c)and cardiovascular disease risk factors,including systolic blood pressure,diastolic blood pressure,triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol,total cholesterol,and body weight.The secondary outcomes included quality of life,self-efficacy,self-care skills,and psychological outcomes.Results:Health coaching intervention has a significant effect on HbA1c[mean difference(MD)=-0.35,confidence interval(CI)=-0.47,-0.22,I2=83%,P<0.001]and HDL-C(MD=-0.50,CI=-0.93,-0.07,I2=10%,P=0.02).The most effective strategy for health coaching delivery associated with improvement of HbA1c was decreasing the number of sessions and increasing the duration of each session.However,no significant difference was found for weight,SBP,diastolic blood pressure,triglyceride,low-density lipoprotein cholesterol,or total cholesterol.Mixed results were reported for the effect of health coaching on quality of life,self-efficacy,self-care skills,and depressive symptoms outcome.Conclusion:Health coaching intervention has a significant effect on HbA1c and HDL-C,and the most effective strategy is decreasing the number of sessions while increasing session duration.However,these results should be interpreted with caution as the evidence comes from studies at some risk of bias with considerable heterogeneity and imprecision.展开更多
A new class of RNA regulatory genes known as microRNAs(miRNAs)has been found to introduce a whole new layer of gene regulation in eukaryotes.The intensive studies of the past several years have demonstrated that miRNA...A new class of RNA regulatory genes known as microRNAs(miRNAs)has been found to introduce a whole new layer of gene regulation in eukaryotes.The intensive studies of the past several years have demonstrated that miRNAs are not only found intracellularly,but are also detectable outside cells,including in various body fluids(e.g.serum,plasma,saliva,urine and milk).This phenomenon raises questions about the biological function of such extracellular miRNAs.Substantial amounts of extracellular miRNAs are enclosed in small membranous vesicles(e.g.exosomes,shedding vesicles and apoptotic bodies)or packaged with RNA-binding proteins(e.g.high-density lipoprotein,Argonaute 2 and nucleophosmin 1).These miRNAs may function as secreted signaling molecules to influence the recipient cell phenotypes.Furthermore,secreted extracellular miRNAs may reflect molecular changes in the cells from which they are derived and can therefore potentially serve as diagnostic indicators of disease.Several studies also point to the potential application of siRNA/miRNA delivery as a new therapeutic strategy for treating diseases.In this review,we summarize what is known about the mechanism of miRNA secretion.In addition,we describe the pathophysiological roles of secreted miRNAs and their clinical potential as diagnostic biomarkers and therapeutic drugs.We believe that miRNA transfer between cells will have a significant impact on biological research in the coming years.展开更多
基金Supported by Grants-in-Aid for scientific research from the Japan Society for the Promotion of Science,No.20015008,20054003,and 21390016
文摘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.
文摘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.
基金supported by a grant from the Scientific Research Foundation for the Returned Overseas Chinese Scholars by the State Education Ministry of China (No.2005383-6144)
文摘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.
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.
基金Project(Nos.PW 55/09 and DS 41/10) supported by the Department of Laboratory Diagnostics,Medical University of Lublin,Poland
文摘Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.
基金Supported by the Graduates’Innovation Fund,Huazhong University of Science and Technology,No.2020yjsCXCY080the Free Innovation Preresearch Fund and Platform Scientific Research Fund in 2019,No.02.03.2019-111.
文摘BACKGROUND At present,the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited.AIM To evaluate the value of a novel parameter for colorectal cancer(CRC)prognosis scoring based on preoperative serum lipid levels.METHODS Four key serum lipid factors,namely,high-density lipoprotein cholesterol(HDLC),low-density lipoprotein cholesterol(LDL-C),apolipoprotein A1(Apo A1),and apolipoprotein B(Apo B),were detected.Two representative ratios,HDL-C-LDLC ratio(HLR)and Apo A1-Apo B ratio(ABR)were calculated.The relationship of these parameters with the prognosis of CRC patients including progression-free survival(PFS)and overall survival(OS)was analyzed by Kaplan-Meier plot and Cox proportional hazards regression.A novel lipoprotein cholesterol-apolipoprotein(LA)score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored.RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C,Apo A1,HLR,and ABR were positively associated with the prognosis of CRC patients.LA score was independently associated with a good prognosis in resectable CRC patients.Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores.CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.
文摘、Background:Using health coaching to improve the quality of life and health outcomes of the patients with diabetes mellitus,has emerged as a possible intervention.However,the few published randomized controlled trials using health coaching for patients with diabetes mellitus have reported mixed results.The present meta-analysis aimed to determine the effectiveness of health coaching on modifying health status and quality of life among diabetic patients and to clarify the characteristics of coaching delivery that make it most effective.Methods:This study searched for articles on randomized controlled trials of health coaching interventions targeting type 2 diabetic patients that were published in the English language from January 2005 through December 2018 in the Cochrane,Medline,PubMed,Trip,and Embase databases.Patients in the control group received usual diabetes mellitus care,and those in the experimental group received health coaching based on usual diabetes mellitus care.The primary outcomes included Hemoglobin A1c(HbA1c)and cardiovascular disease risk factors,including systolic blood pressure,diastolic blood pressure,triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol,total cholesterol,and body weight.The secondary outcomes included quality of life,self-efficacy,self-care skills,and psychological outcomes.Results:Health coaching intervention has a significant effect on HbA1c[mean difference(MD)=-0.35,confidence interval(CI)=-0.47,-0.22,I2=83%,P<0.001]and HDL-C(MD=-0.50,CI=-0.93,-0.07,I2=10%,P=0.02).The most effective strategy for health coaching delivery associated with improvement of HbA1c was decreasing the number of sessions and increasing the duration of each session.However,no significant difference was found for weight,SBP,diastolic blood pressure,triglyceride,low-density lipoprotein cholesterol,or total cholesterol.Mixed results were reported for the effect of health coaching on quality of life,self-efficacy,self-care skills,and depressive symptoms outcome.Conclusion:Health coaching intervention has a significant effect on HbA1c and HDL-C,and the most effective strategy is decreasing the number of sessions while increasing session duration.However,these results should be interpreted with caution as the evidence comes from studies at some risk of bias with considerable heterogeneity and imprecision.
基金by grants from the National Natural Science Foundation of China(Nos.90813035,81101330,81171661,30890044,30772484,30725008,30890032,31071232,31000323,90608010,and J1103512)the Natural Science Foundation of Jiangsu Province(No.BK2011013)the Fundamental Research Funds for the Central Universities(No.1107020839).
文摘A new class of RNA regulatory genes known as microRNAs(miRNAs)has been found to introduce a whole new layer of gene regulation in eukaryotes.The intensive studies of the past several years have demonstrated that miRNAs are not only found intracellularly,but are also detectable outside cells,including in various body fluids(e.g.serum,plasma,saliva,urine and milk).This phenomenon raises questions about the biological function of such extracellular miRNAs.Substantial amounts of extracellular miRNAs are enclosed in small membranous vesicles(e.g.exosomes,shedding vesicles and apoptotic bodies)or packaged with RNA-binding proteins(e.g.high-density lipoprotein,Argonaute 2 and nucleophosmin 1).These miRNAs may function as secreted signaling molecules to influence the recipient cell phenotypes.Furthermore,secreted extracellular miRNAs may reflect molecular changes in the cells from which they are derived and can therefore potentially serve as diagnostic indicators of disease.Several studies also point to the potential application of siRNA/miRNA delivery as a new therapeutic strategy for treating diseases.In this review,we summarize what is known about the mechanism of miRNA secretion.In addition,we describe the pathophysiological roles of secreted miRNAs and their clinical potential as diagnostic biomarkers and therapeutic drugs.We believe that miRNA transfer between cells will have a significant impact on biological research in the coming years.
