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
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
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
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
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 Sout...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,apo- lipoproteins 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
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 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
Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum trigly...Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum triglyceride, de-creased high-density lipoprotein cholesterol (HDL-C ) and apolipoprotein A-I(Apo A-I ), whi1e CAPD patients had elevated total cho1esterol, triglyceride,low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-Iratio, and decreased HDL-C, Apo A-I. Because of the molecular sievingeffects of peritoneum, CAPD have a negative effect on these abnormalities. CAPDpatients might be at greater risk of developing coronary artery disease than HD patients who are also at increased riskas compared with normals.展开更多
Whereas the close structural homology between human plasminogen and apolipoprotein(a) has been known for a number of years only recent studies have revealed that both proteins carry linked oxidized phospholipids that ...Whereas the close structural homology between human plasminogen and apolipoprotein(a) has been known for a number of years only recent studies have revealed that both proteins carry linked oxidized phospholipids that may modify the function of these proteins. Future studies should provide a better understanding of oxidized phospholipid adducts and the role played by lipoprotein-associated phospholipase A2 for which cleavage specificity has been established when these modified lipids are in a free form.展开更多
Objective PERK/eI F2α/CHOP is a major signaling pathway mediating endoplasmic reticulum(ER) stress related with atherosclerosis.Oxidized LDL(ox-LDL) also induces endothelial apoptosis and plays a vital role in the in...Objective PERK/eI F2α/CHOP is a major signaling pathway mediating endoplasmic reticulum(ER) stress related with atherosclerosis.Oxidized LDL(ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis.The present study was conducted to explore the regulatory effect of ox-LDL on PERK/e IF2α/CHOP signaling pathway in vascular endothelial cells.Methods The effects of ox-LDL on PERK and p-e IF2α protein expression of primary human umbilical vein endothelial cells(HUVECs) were investigated by Western blot analysis.PERK gene silencing and selective eI F2α phosphatase inhibitor,salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis,caspase-3 activity,and CHOP mR NA level.Results Ox-LDL treatment significantly increased the expression of PERK,PERK-mediated inactivation of e IF2α phosphorylation,and the expression of CHOP,as well as the caspase-3 activity and apoptosis.The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral sh RNA or by selective eI F2α phosphatase inhibitor,salubrinal.Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eI F2α/CHOP ER-stress pathway.It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.展开更多
AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. ...AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. METHODS: A cross sectional study was performed that enrolled 144 subjects with type 2 diabetes mellitus above the age of 25 years attending outpatient clinic of Government Medical College, Kozhikode. Lp(a) levels were measured quantitatively in venous samples using Turbidimetric Immunoassay in all subjects. Each patient was evaluated for micro vascular complications, namely diabetic retinopathy, nephropathy and neuropathy. The relationship between Lp(a) levels and the micro vascular complications was assessed by univariate analysis. RESULTS: Mean age of cases was 53.93 ± 10.74 years with a male to female ratio of 1.3:1. Mean duration of diabetes was 9.53 ± 7.3 years. Abnormal Lp(a) levels (≥ 30 mg/dL) were observed in 38 (26.4%) diabetic subjects. Seventy-eight (54.16%) cases had diabetic nephropathy and significantly higher Lp(a) levels were found among these cases [Median 28.2 mg/dL (Interquartile range; IQR 24.4-33.5) vs 19.3 mg/dL (IQR 14.7-23.5); P < 0.05]. Retinopathy was present among 66 (45.13%) cases and peripheral neuropathy was detected among 54 (37.5%) cases. However, Lp(a) levels were not significantly different among those with or without retinopathy and neuropathy. Positive correlation was found between higher Lp(a) levels and duration of diabetes (r = 0.165, P < 0.05) but not with HbA1c values (r = - 0.083). CONCLUSION: Abnormal Lp(a) levels were found among 26.4% of diabetic subjects. Patients with diabetic nephropathy had higher Lp(a) levels. No association was found between Lp(a) levels and diabetic retinopathy or neuropathy. Longer duration of diabetes correlated with higher Lp(a) levels.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
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.
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.
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.
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,apo- lipoproteins 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.
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.
文摘Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum triglyceride, de-creased high-density lipoprotein cholesterol (HDL-C ) and apolipoprotein A-I(Apo A-I ), whi1e CAPD patients had elevated total cho1esterol, triglyceride,low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-Iratio, and decreased HDL-C, Apo A-I. Because of the molecular sievingeffects of peritoneum, CAPD have a negative effect on these abnormalities. CAPDpatients might be at greater risk of developing coronary artery disease than HD patients who are also at increased riskas compared with normals.
文摘Whereas the close structural homology between human plasminogen and apolipoprotein(a) has been known for a number of years only recent studies have revealed that both proteins carry linked oxidized phospholipids that may modify the function of these proteins. Future studies should provide a better understanding of oxidized phospholipid adducts and the role played by lipoprotein-associated phospholipase A2 for which cleavage specificity has been established when these modified lipids are in a free form.
基金State Key Clinical Specialty Construction Project,China
文摘Objective PERK/eI F2α/CHOP is a major signaling pathway mediating endoplasmic reticulum(ER) stress related with atherosclerosis.Oxidized LDL(ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis.The present study was conducted to explore the regulatory effect of ox-LDL on PERK/e IF2α/CHOP signaling pathway in vascular endothelial cells.Methods The effects of ox-LDL on PERK and p-e IF2α protein expression of primary human umbilical vein endothelial cells(HUVECs) were investigated by Western blot analysis.PERK gene silencing and selective eI F2α phosphatase inhibitor,salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis,caspase-3 activity,and CHOP mR NA level.Results Ox-LDL treatment significantly increased the expression of PERK,PERK-mediated inactivation of e IF2α phosphorylation,and the expression of CHOP,as well as the caspase-3 activity and apoptosis.The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral sh RNA or by selective eI F2α phosphatase inhibitor,salubrinal.Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eI F2α/CHOP ER-stress pathway.It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
文摘AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes mellitus patients and to determine the relationship between Lp(a) in type 2 diabetes mellitus patients and micro-vascular complications. METHODS: A cross sectional study was performed that enrolled 144 subjects with type 2 diabetes mellitus above the age of 25 years attending outpatient clinic of Government Medical College, Kozhikode. Lp(a) levels were measured quantitatively in venous samples using Turbidimetric Immunoassay in all subjects. Each patient was evaluated for micro vascular complications, namely diabetic retinopathy, nephropathy and neuropathy. The relationship between Lp(a) levels and the micro vascular complications was assessed by univariate analysis. RESULTS: Mean age of cases was 53.93 ± 10.74 years with a male to female ratio of 1.3:1. Mean duration of diabetes was 9.53 ± 7.3 years. Abnormal Lp(a) levels (≥ 30 mg/dL) were observed in 38 (26.4%) diabetic subjects. Seventy-eight (54.16%) cases had diabetic nephropathy and significantly higher Lp(a) levels were found among these cases [Median 28.2 mg/dL (Interquartile range; IQR 24.4-33.5) vs 19.3 mg/dL (IQR 14.7-23.5); P < 0.05]. Retinopathy was present among 66 (45.13%) cases and peripheral neuropathy was detected among 54 (37.5%) cases. However, Lp(a) levels were not significantly different among those with or without retinopathy and neuropathy. Positive correlation was found between higher Lp(a) levels and duration of diabetes (r = 0.165, P < 0.05) but not with HbA1c values (r = - 0.083). CONCLUSION: Abnormal Lp(a) levels were found among 26.4% of diabetic subjects. Patients with diabetic nephropathy had higher Lp(a) levels. No association was found between Lp(a) levels and diabetic retinopathy or neuropathy. Longer duration of diabetes correlated with higher Lp(a) levels.
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.
