BACKGROUND Young-onset type 2 diabetes mellitus(T2DM)is associated with adverse health outcomes and increased mortality.Vitamin D(VitD)deficiency is likewise linked to various adverse health outcomes and is significan...BACKGROUND Young-onset type 2 diabetes mellitus(T2DM)is associated with adverse health outcomes and increased mortality.Vitamin D(VitD)deficiency is likewise linked to various adverse health outcomes and is significantly associated with lipid metabolism in patients with T2DM.However,little is known regarding the me-chanisms of interaction between VitD and apolipoprotein A1(apoA1)in young-onset T2DM.AIM To evaluate the relationship between VitD and apoA1 levels in patients with young-onset T2DM.METHODS This cross-sectional study was conducted at Zhejiang Provincial People’s Hospital between January 2019 and December 2023.A total of 642 patients with T2DM who aged 18-40 years were included and matched with 642 individuals without diabetes(controls)based on age and sex.No specific intervention was applied,and data were collected from medical records and laboratory tests.The re-lationship between VitD and apoA1 levels was examined using Spearman’s correlation and logistic regression models.RESULTS We found that VitD levels were significantly lower in patients with T2DM compared to controls(15.9 ng/mL vs 17.4 ng/mL,P<0.001),with a notable positive correlation between VitD deficiency and reduced apoA1 levels.Multifactor logistic regression analysis identified that severe VitD deficiency was an independent risk factor for apoA1 in young-onset T2DM patients(odds ratio=3.43,95%confidence interval:1.16-10.20,β=1.23,P=0.026).CONCLUSION Our findings reveal an association between VitD and apoA1 in young-onset T2DM,suggesting that VitD may play a crucial role in metabolic regulation and cardiovascular risk management.展开更多
Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a...Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.展开更多
This study investigated the association of apolipoprotein A5 （apoA5） gene polymorphism at position -1131T〉C with cerebral infarction in patients with type 2 diabetes. A total of 256 type 2 diabetic patients without...This study investigated the association of apolipoprotein A5 （apoA5） gene polymorphism at position -1131T〉C with cerebral infarction in patients with type 2 diabetes. A total of 256 type 2 diabetic patients without cerebral infarction （T2DM）, 220 type 2 diabetic patients with cerebral infarction （T2DMCI） and 340 healthy subjects were recruited from the same region （Hubei province, China）. The genotype of apoA5 -1131T〉C was analyzed by polymerase chain reaction, followed by restriction fragment length polymorphism （PCR-RFLP）. Total cholesterol, HDL cholesterol, LDL-cholesterol and triglycerides were quantitatively detected by using standard enzymatic tech- niques. The results showed that the prevalence of the apoA5 -1131C allele was significantly higher in T2DMCI group than that in control group （42.7% versus 31.2%, P〈0.01）. The carriers of rare C allele had higher TG levels as compared with carriers of common allele in the three groups （P〈0.01）. Logistic regression models, which were adjusted for age, gender, blood pressure, BMI, FBS, smoking, LDL-C and HDL-C, revealed that patients carrying the apoA5 -1131C allele and CC homozygotes were at high risk for T2DMCI. It was concluded that the apoA5 -1131C allele variant is an independent genetic risk factor for T2DMCI.展开更多
Although localized prostate cancer(PCa)can be cured by prostatectomy and radiotherapy,the development of effective therapeutic approaches for advanced prostate cancer,including castration-resistant PCa(CRPC)and neuroe...Although localized prostate cancer(PCa)can be cured by prostatectomy and radiotherapy,the development of effective therapeutic approaches for advanced prostate cancer,including castration-resistant PCa(CRPC)and neuroendocrine PCa(NEPC),is lagging far behind.Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need.Here,we report that apolipoprotein A-I(ApoA-I),the major component of high-density lipoprotein(HDL),is upregulated in PCa based on both bioinformatics and experimental evidence.The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells.Molecularly,ApoA-I is regulated by MYC,a frequently amplified oncogene in late-stage PCa.Altogether,our findings have revealed a novel indicator to predict prognosis and recurrence,which would benefit patients who are prone to progress to metastasis or even NEPC,which is the lethal subtype of PCa.展开更多
Background： Several studies have reported that apolipoprotein A5 （APOA5） is involved in the development of non-alcoholic fatty liver disease （NAFLD）. However, no research has been performed regardingthe associati...Background： Several studies have reported that apolipoprotein A5 （APOA5） is involved in the development of non-alcoholic fatty liver disease （NAFLD）. However, no research has been performed regardingthe association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore theassociation between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.展开更多
Objectives Apolipoprotein(Apo)A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG)levels,but little is known about their interactions on serum lipid levels.The pres...Objectives Apolipoprotein(Apo)A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG)levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol(TC),TG,high-density lipoprotein cholesterol(HDL-C),ApoA1 and ApoB were higher in drinkers than in nondrinkers(P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs)were not different between the two groups.The levels of TG in non-drinkers,and TC,TG,low-density lipoprotein cholesterol(LDL-C)and ApoB in drinkers were different among the three-1131T】C genotypes(P【0.05-0.001).The-1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all),but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types(P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T,G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05)associated at the global level with TC,TG,HDL-C,LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with-1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with-1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and-1131T】C,c.553G】T and c.457G】A to detect the interactions of the ApoA5 gene.展开更多
AIM:To investigate the anti-angiogenic effect of apolipoprotein A1(apoA1)on primary human retinal vascular endothelial cells(HRECs)and explore the possible mechanism.METHODS:The primary HRECs were transfected with apo...AIM:To investigate the anti-angiogenic effect of apolipoprotein A1(apoA1)on primary human retinal vascular endothelial cells(HRECs)and explore the possible mechanism.METHODS:The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors.Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition.The concentrations of secreted vascular endothelial growth factor(VEGF)and placental growth factor(PlGF)were measured by enzyme-linked immunosorbent assay(ELISA).Cell migration ability was detected by wound healing assay.The sprouting of HRECs was determined by tube formation assay.The protein levels of extracellular signal regulated kinase 1/2(ERK1/2)and phosphor ylated ERK1/2(p-ERK1/2)were measured by Western blot.RESULTS:Overexpressed apoA1 in hypoxia-induced HRECs significantly suppressed PlGF(0.67±0.10 folds,P=0.007).Overexpressed apoA1 also attenuated hypoxiainduced cell migration(0.32±0.11 folds,P<0.0001),tube formation(0.66±0.01 folds,P<0.0001)and the phosphorylation levels of ERK(0.6±0.11 folds,P=0.025).Pretreatment of mitogen-activated protein kinase kinase(MEK)inhibitor(U0126)further reduced the PlGF and angiogenesis in hypoxia-induced HRECs.CONCLUSION:ApoA 1 inhibits the angiogenesis at least in part by inactivating ERK1/2 in hypoxia-induced HRECs.Moreover,apoA1 suppresses the PlGF expression,which selectively associated with pathological angiogenesis.展开更多
Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and...Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and difficulty of purifying the protein and producing the highly effective dimeric form.The aim of this study was to create an expression cassette that specifically drives the expression of dimeric ApoA-IM in the protein bodies of rice seeds.The ApoA-IM protein under control of the 13 kDa prolamin promoter is expressed exclusively in its dimeric form within the seeds,and immunocytochemical and immunogold analyses confirmed its expression in different caryopsis tissue such as seed coat,aleurone cell and endosperm,particularly in amyloplast and storage vacuoles.A plant-based ApoA-IM production system offered numerous advantages over current production systems,including the direct production of the most therapeutically effective dimeric ApoA-IM forms,long-term protein storage in seeds,and ease of protein production by simply growing plants.Therefore,seeds had the potential to serve as a costeffective source of therapeutic ApoA-IM.展开更多
Background Studies have shown that the apt （a） gene （LPA） rs3798220 polymorphism is associated with thelevels of lipids and the curative effect of statin therapy for carotid atherosclerosis （CAS）. Whether carrie...Background Studies have shown that the apt （a） gene （LPA） rs3798220 polymorphism is associated with thelevels of lipids and the curative effect of statin therapy for carotid atherosclerosis （CAS）. Whether carriers ofan apt （a） variant benefit more from statin remains unclear. Methods One hundred and three patients with CAS were recruited from April 2012 to April 2013 in the Shunde First People＇s Hospital Affiliated to Southern Medical University in Foshan. All patients were administered atorvastatin 20 mg/d and were followed-up for 2 years, with the levels of plasma Lp （a）, total cholesterol （TC）, triglyceride （TG）, high density lipoprotein （HDL）, low density lipoprotein （LDL）. LPA rs3798220 genotypes of all patients were analyzed. Results Statin treatment significantly reduced the levels of IMT, TC, TG, LDL and increased the level of HDL, but statin treatment did not reduce the level ofLp （a）. According to the curative effect of statin therapy in patients with CAS, rs3798220 polymorphism had a certain influence on LDL and TC levels, but not on the improvement of the IMT, TG, HDL and Lp （a）. Conclusion Rs 3798220 polymorphism has a certain impact on the curative effects of statin, on LDL and TC levels.展开更多
Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilit...Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.展开更多
Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed...Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed to determine the association of HDL-C/apo A-I ratio with the severity of coronary artery lesions in diabetic patients.Methods Observational study was conducted and 478 diabetic patients with acute coronary syndrome(ACS)were enrolled.Baseline serum levels of HDL-C,apo A-I,clinical and biochemical parameters were collected.All patients underwent coronary angiography to evaluate the severity of coronary artery disease(CAD)in terms of the number of stenotic coronary arteries(defined as a stenosis≥50%)and the calculated Gensini score.Patients were then divided into different subgroups according to the two categories:single-,double-or triple-vessel groups;and Gensini Score groups(lower≤4,middle:5-15,and upper≥16).Receiver operating characteristic curves(ROC)were conducted to evaluate the diagnostic values in identifying severe CAD lesions.The association between HDL-C/apo A-I ratio and CAD severity was determined by multivariate logistic regression analysis.Results Patients with triple-vessel lesions or upper Gensini score had more CAD risk factors such as older age,smoking,low HDL-C and elevated fasting blood glucose(FBG).A lower HDL-C/apo A-I ratio corresponded to more vessels stenoses and a higher Gensini score.Notably,HDL-C/apo A-I outperformed HDL-C or apo A-I alone in diagnosing severe CAD lesions in ROC analyses.Moreover,multivariate regression analyses revealed that after adjustment for traditional risk factors such as LDL-C,FBG and HAb1c,HDL-C/apo A-I ratio remained independently associated with the severity of CAD in diabetic patients with ACS(all P<0.05).Conclusions HDL-C/apo A-I may be a useful indicator for the severity of CAD in diabetic patients with ACS.展开更多
Objective To analyze the relationship between polymorphism at the Apolipoprotein AI (Apo AI) gene and the risk for coronary artery disease. Methods A total of 107 patients (mean age 56 ±11 years) diagnosed as hav...Objective To analyze the relationship between polymorphism at the Apolipoprotein AI (Apo AI) gene and the risk for coronary artery disease. Methods A total of 107 patients (mean age 56 ±11 years) diagnosed as having stable angina pectoris (SAP) (23 cases), unstable angina pectoris (UAP) (23 cases) or myocardial infarction (MI) (61 cases) were prospectively evaluated. DNA was obtained from the 107 patients and 50 controls. In order to determine the Apo AI genotypes at two polymorphic sites (G/A at -75 bp, and C/T at+83 bp), DNA was PCR amplified and digested with MspI. Results The frequency of carriers of the rare allele at the - 75 bp site (M1-) was 0.49 in cases and 0.30 in controls (P<0. 05). The frequencies of the M1-allele among patients with SAP, UAP, MI and controls were 0. 37 (vs. controls, P > 0. 05), 0.54 (vs. controls, P < 0.05), 0.52 (vs. controls, P<0. 05) and 0. 30, respectively. The frequencies for carriers of the rare allele at the + 83bp polymorphism (M2) were observed among patients with SAP (0. 09, vs. controls, P > 0.05), UAP (0.11, vs. controls, P>0.05) or MI (0. 12, vs. controls, P>0. 05) and controls (0. 12). There was an slightly increase in the frequency of the Ml - allele in patients with SAP to UAP or MI (0. 37 vs. 0. 54 vs. 0. 52; all P>0. 05) and Ml polymorphism as a risk factor for CAD ( OR = 3. 74, P < 0. 05). In the + 83bp polymorphism there was no difference in the allelelic frequencies in cases and controls (0. 11 vs. 0. 12; P > 0. 05). There was no significantdifference in the frequency of the M2 - allele in patients with SAP to UAP or MI (0.09 vs. 0. 11 vs. 0. 12; all P>0. 05) and M2 polymorphism not as a factor for CAD (OR=0.80, P>0. 05).Plasma lipoprotein values in patients with the allele M1-and M2 - had no different levels than those homozygous for the M1+and M2+(P>0.05). Conclusion Ml polymorphism (M1 - ) may be as a risk factor for CAD and M2 polymorphism (M2 - ) not as a factor for CAD in Chinese Xinjiang Uygur and Han population.展开更多
Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized...Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticles.展开更多
Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld...Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.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
Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary...Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.展开更多
The serum apolipoprotein A- I (apo A-I) Concentrations in 39 patients with posthepatitis cirrhosis were reported to be 0.87±0.27 g/L lower than that of controls 1.15±0.14 g/L P【0.01. The, decrease of apo. A...The serum apolipoprotein A- I (apo A-I) Concentrations in 39 patients with posthepatitis cirrhosis were reported to be 0.87±0.27 g/L lower than that of controls 1.15±0.14 g/L P【0.01. The, decrease of apo. A-I was correlated with the severityof impaired liver function. Apo A- I concentrations in serum correlated positively with decrease of serum albumin (r=0.503 P【 0.01) and negatively with serum bilirubin increase (r=- 0.508 P 【0.01) . The data indicate that decreasing of apo A- I concentration may be regarded as one of the reliable indices reflecting the degree of liver function impairment.展开更多
Objective:To explore the association between lipoprotein and arteriosclerosis in hospitalized and outpatient populations in western Beijing.Methods:Patients enrolled in the outpatient department and hospitalization fr...Objective:To explore the association between lipoprotein and arteriosclerosis in hospitalized and outpatient populations in western Beijing.Methods:Patients enrolled in the outpatient department and hospitalization from January 2013 to December 2017 were selected and eventually 258 cases were included in the study according to strict enrollment and exclusion criteria. The data were true and reliable. Statistically, an independent sample t-test and correlation analysis method were used, and the receiver operating characteristic curve was plotted using the predicted values of apolipoprotein A1 and apolipoprotein B for arteriosclerosis by controlling confounding factors.Results: Correlation analysis showed that there was a significant correlation between apolipoprotein B (P=0.007, correlation coefficient: -0.203) and carotid-femoral pulse wave velocity. Apolipoprotein A1 and apolipoprotein B had a strong diagnostic value for arteriosclerosis in patients without coronary heart disease. Conclusions: There is a significant negative correlation between apolipoprotein B and carotid-pulse wave velocity in the unconflicted patients in this study. Apolipoprotein A1 and apolipoprotein B have diagnostic value for arteriosclerosis.展开更多
Mice overexpressing the human apolipoprotein apo CIII are a model of dyslipidemia. They become hypertxiglyceridemic, hypercholesterolemic and have high blood levels of free fatty acids. Blood glucose is normal, but as...Mice overexpressing the human apolipoprotein apo CIII are a model of dyslipidemia. They become hypertxiglyceridemic, hypercholesterolemic and have high blood levels of free fatty acids. Blood glucose is normal, but as the liver integrates lipid and carbohydrate metabolism, conditions of high inter-tissue circulation of energy substxates, such as fasting, may reveal hepatic alterations of glucose metabolism in these （CIII） mice. This hypothesis was explored by in situ liver perfusion in this investigation. The NTG （non-txansgenic） animals showed liver and muscle glycogen content changes compatible with the fed or fasted state. In contrast, glycogen in group CIII was much lower in the fed state. The liver glucose release in group CIII after overnight fasting and adrenaline-stimulated was lower than in group NTG. Total glucose production under gluconeogenic conditions was not different between groups NTG and CIII, but glucose production from alanine was decreased in group CIII. Therefore, dyslipidemia caused by overexpression of apoCIII in mice alters the liver glucose metabolism, particularly compromising glycogen synthesis and degradation. This profile might have adverse outcomes during metabolic challenges that are more severe than fasting.展开更多
Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hep...Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.展开更多
基金Supported by the Medical Science and Technology Project of Zhejiang Province,No.2022KY518General Scientific Research Project of Zhejiang Provincial Education Department,No.Y202352799Medical Science and Technology Project of Zhejiang Province,No.2024KY726.
文摘BACKGROUND Young-onset type 2 diabetes mellitus(T2DM)is associated with adverse health outcomes and increased mortality.Vitamin D(VitD)deficiency is likewise linked to various adverse health outcomes and is significantly associated with lipid metabolism in patients with T2DM.However,little is known regarding the me-chanisms of interaction between VitD and apolipoprotein A1(apoA1)in young-onset T2DM.AIM To evaluate the relationship between VitD and apoA1 levels in patients with young-onset T2DM.METHODS This cross-sectional study was conducted at Zhejiang Provincial People’s Hospital between January 2019 and December 2023.A total of 642 patients with T2DM who aged 18-40 years were included and matched with 642 individuals without diabetes(controls)based on age and sex.No specific intervention was applied,and data were collected from medical records and laboratory tests.The re-lationship between VitD and apoA1 levels was examined using Spearman’s correlation and logistic regression models.RESULTS We found that VitD levels were significantly lower in patients with T2DM compared to controls(15.9 ng/mL vs 17.4 ng/mL,P<0.001),with a notable positive correlation between VitD deficiency and reduced apoA1 levels.Multifactor logistic regression analysis identified that severe VitD deficiency was an independent risk factor for apoA1 in young-onset T2DM patients(odds ratio=3.43,95%confidence interval:1.16-10.20,β=1.23,P=0.026).CONCLUSION Our findings reveal an association between VitD and apoA1 in young-onset T2DM,suggesting that VitD may play a crucial role in metabolic regulation and cardiovascular risk management.
基金supported by the National Natural Science Foundation of China(grant Nos.30972531 and 81320108026)a project of the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.
文摘This study investigated the association of apolipoprotein A5 （apoA5） gene polymorphism at position -1131T〉C with cerebral infarction in patients with type 2 diabetes. A total of 256 type 2 diabetic patients without cerebral infarction （T2DM）, 220 type 2 diabetic patients with cerebral infarction （T2DMCI） and 340 healthy subjects were recruited from the same region （Hubei province, China）. The genotype of apoA5 -1131T〉C was analyzed by polymerase chain reaction, followed by restriction fragment length polymorphism （PCR-RFLP）. Total cholesterol, HDL cholesterol, LDL-cholesterol and triglycerides were quantitatively detected by using standard enzymatic tech- niques. The results showed that the prevalence of the apoA5 -1131C allele was significantly higher in T2DMCI group than that in control group （42.7% versus 31.2%, P〈0.01）. The carriers of rare C allele had higher TG levels as compared with carriers of common allele in the three groups （P〈0.01）. Logistic regression models, which were adjusted for age, gender, blood pressure, BMI, FBS, smoking, LDL-C and HDL-C, revealed that patients carrying the apoA5 -1131C allele and CC homozygotes were at high risk for T2DMCI. It was concluded that the apoA5 -1131C allele variant is an independent genetic risk factor for T2DMCI.
基金This work is supported by the National Natural Science Foundation of China(No.81630019,81902611,and 81672522)Anhui Natural Science Foundation(1908085QH337).
文摘Although localized prostate cancer(PCa)can be cured by prostatectomy and radiotherapy,the development of effective therapeutic approaches for advanced prostate cancer,including castration-resistant PCa(CRPC)and neuroendocrine PCa(NEPC),is lagging far behind.Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need.Here,we report that apolipoprotein A-I(ApoA-I),the major component of high-density lipoprotein(HDL),is upregulated in PCa based on both bioinformatics and experimental evidence.The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells.Molecularly,ApoA-I is regulated by MYC,a frequently amplified oncogene in late-stage PCa.Altogether,our findings have revealed a novel indicator to predict prognosis and recurrence,which would benefit patients who are prone to progress to metastasis or even NEPC,which is the lethal subtype of PCa.
基金supported by the grant of National Natural Science Foundation of China(31770837)
文摘Background： Several studies have reported that apolipoprotein A5 （APOA5） is involved in the development of non-alcoholic fatty liver disease （NAFLD）. However, no research has been performed regardingthe association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore theassociation between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.
文摘Objectives Apolipoprotein(Apo)A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG)levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol(TC),TG,high-density lipoprotein cholesterol(HDL-C),ApoA1 and ApoB were higher in drinkers than in nondrinkers(P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs)were not different between the two groups.The levels of TG in non-drinkers,and TC,TG,low-density lipoprotein cholesterol(LDL-C)and ApoB in drinkers were different among the three-1131T】C genotypes(P【0.05-0.001).The-1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all),but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types(P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T,G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05)associated at the global level with TC,TG,HDL-C,LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with-1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with-1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and-1131T】C,c.553G】T and c.457G】A to detect the interactions of the ApoA5 gene.
基金Supported by the National Natural Science Foundation of China(No.81500735,No.81970807)。
文摘AIM:To investigate the anti-angiogenic effect of apolipoprotein A1(apoA1)on primary human retinal vascular endothelial cells(HRECs)and explore the possible mechanism.METHODS:The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors.Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition.The concentrations of secreted vascular endothelial growth factor(VEGF)and placental growth factor(PlGF)were measured by enzyme-linked immunosorbent assay(ELISA).Cell migration ability was detected by wound healing assay.The sprouting of HRECs was determined by tube formation assay.The protein levels of extracellular signal regulated kinase 1/2(ERK1/2)and phosphor ylated ERK1/2(p-ERK1/2)were measured by Western blot.RESULTS:Overexpressed apoA1 in hypoxia-induced HRECs significantly suppressed PlGF(0.67±0.10 folds,P=0.007).Overexpressed apoA1 also attenuated hypoxiainduced cell migration(0.32±0.11 folds,P<0.0001),tube formation(0.66±0.01 folds,P<0.0001)and the phosphorylation levels of ERK(0.6±0.11 folds,P=0.025).Pretreatment of mitogen-activated protein kinase kinase(MEK)inhibitor(U0126)further reduced the PlGF and angiogenesis in hypoxia-induced HRECs.CONCLUSION:ApoA 1 inhibits the angiogenesis at least in part by inactivating ERK1/2 in hypoxia-induced HRECs.Moreover,apoA1 suppresses the PlGF expression,which selectively associated with pathological angiogenesis.
文摘Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and difficulty of purifying the protein and producing the highly effective dimeric form.The aim of this study was to create an expression cassette that specifically drives the expression of dimeric ApoA-IM in the protein bodies of rice seeds.The ApoA-IM protein under control of the 13 kDa prolamin promoter is expressed exclusively in its dimeric form within the seeds,and immunocytochemical and immunogold analyses confirmed its expression in different caryopsis tissue such as seed coat,aleurone cell and endosperm,particularly in amyloplast and storage vacuoles.A plant-based ApoA-IM production system offered numerous advantages over current production systems,including the direct production of the most therapeutically effective dimeric ApoA-IM forms,long-term protein storage in seeds,and ease of protein production by simply growing plants.Therefore,seeds had the potential to serve as a costeffective source of therapeutic ApoA-IM.
基金supported by Science and Technology Planning Project of Foshan city(No.201108190)
文摘Background Studies have shown that the apt （a） gene （LPA） rs3798220 polymorphism is associated with thelevels of lipids and the curative effect of statin therapy for carotid atherosclerosis （CAS）. Whether carriers ofan apt （a） variant benefit more from statin remains unclear. Methods One hundred and three patients with CAS were recruited from April 2012 to April 2013 in the Shunde First People＇s Hospital Affiliated to Southern Medical University in Foshan. All patients were administered atorvastatin 20 mg/d and were followed-up for 2 years, with the levels of plasma Lp （a）, total cholesterol （TC）, triglyceride （TG）, high density lipoprotein （HDL）, low density lipoprotein （LDL）. LPA rs3798220 genotypes of all patients were analyzed. Results Statin treatment significantly reduced the levels of IMT, TC, TG, LDL and increased the level of HDL, but statin treatment did not reduce the level ofLp （a）. According to the curative effect of statin therapy in patients with CAS, rs3798220 polymorphism had a certain influence on LDL and TC levels, but not on the improvement of the IMT, TG, HDL and Lp （a）. Conclusion Rs 3798220 polymorphism has a certain impact on the curative effects of statin, on LDL and TC levels.
基金Supported by a grant from NIH(R37-HL64159)an AHA Postdoctoral Fellowship Award(VS)
文摘Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.
基金the National Key Research and Development Program of China(No.2016YFC1301202)National Key Research and Development Program of China(No.2016YFC1301305)。
文摘Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed to determine the association of HDL-C/apo A-I ratio with the severity of coronary artery lesions in diabetic patients.Methods Observational study was conducted and 478 diabetic patients with acute coronary syndrome(ACS)were enrolled.Baseline serum levels of HDL-C,apo A-I,clinical and biochemical parameters were collected.All patients underwent coronary angiography to evaluate the severity of coronary artery disease(CAD)in terms of the number of stenotic coronary arteries(defined as a stenosis≥50%)and the calculated Gensini score.Patients were then divided into different subgroups according to the two categories:single-,double-or triple-vessel groups;and Gensini Score groups(lower≤4,middle:5-15,and upper≥16).Receiver operating characteristic curves(ROC)were conducted to evaluate the diagnostic values in identifying severe CAD lesions.The association between HDL-C/apo A-I ratio and CAD severity was determined by multivariate logistic regression analysis.Results Patients with triple-vessel lesions or upper Gensini score had more CAD risk factors such as older age,smoking,low HDL-C and elevated fasting blood glucose(FBG).A lower HDL-C/apo A-I ratio corresponded to more vessels stenoses and a higher Gensini score.Notably,HDL-C/apo A-I outperformed HDL-C or apo A-I alone in diagnosing severe CAD lesions in ROC analyses.Moreover,multivariate regression analyses revealed that after adjustment for traditional risk factors such as LDL-C,FBG and HAb1c,HDL-C/apo A-I ratio remained independently associated with the severity of CAD in diabetic patients with ACS(all P<0.05).Conclusions HDL-C/apo A-I may be a useful indicator for the severity of CAD in diabetic patients with ACS.
文摘Objective To analyze the relationship between polymorphism at the Apolipoprotein AI (Apo AI) gene and the risk for coronary artery disease. Methods A total of 107 patients (mean age 56 ±11 years) diagnosed as having stable angina pectoris (SAP) (23 cases), unstable angina pectoris (UAP) (23 cases) or myocardial infarction (MI) (61 cases) were prospectively evaluated. DNA was obtained from the 107 patients and 50 controls. In order to determine the Apo AI genotypes at two polymorphic sites (G/A at -75 bp, and C/T at+83 bp), DNA was PCR amplified and digested with MspI. Results The frequency of carriers of the rare allele at the - 75 bp site (M1-) was 0.49 in cases and 0.30 in controls (P<0. 05). The frequencies of the M1-allele among patients with SAP, UAP, MI and controls were 0. 37 (vs. controls, P > 0. 05), 0.54 (vs. controls, P < 0.05), 0.52 (vs. controls, P<0. 05) and 0. 30, respectively. The frequencies for carriers of the rare allele at the + 83bp polymorphism (M2) were observed among patients with SAP (0. 09, vs. controls, P > 0.05), UAP (0.11, vs. controls, P>0.05) or MI (0. 12, vs. controls, P>0. 05) and controls (0. 12). There was an slightly increase in the frequency of the Ml - allele in patients with SAP to UAP or MI (0. 37 vs. 0. 54 vs. 0. 52; all P>0. 05) and Ml polymorphism as a risk factor for CAD ( OR = 3. 74, P < 0. 05). In the + 83bp polymorphism there was no difference in the allelelic frequencies in cases and controls (0. 11 vs. 0. 12; P > 0. 05). There was no significantdifference in the frequency of the M2 - allele in patients with SAP to UAP or MI (0.09 vs. 0. 11 vs. 0. 12; all P>0. 05) and M2 polymorphism not as a factor for CAD (OR=0.80, P>0. 05).Plasma lipoprotein values in patients with the allele M1-and M2 - had no different levels than those homozygous for the M1+and M2+(P>0.05). Conclusion Ml polymorphism (M1 - ) may be as a risk factor for CAD and M2 polymorphism (M2 - ) not as a factor for CAD in Chinese Xinjiang Uygur and Han population.
基金This work was funded by an Irish Research Council for Science,Engineering and Technology Postdoctoral Fellowship(M.L.)the Marianne and Marcus Wallenberg Foundation(M.L.)+2 种基金the EU FP6 project NanoInteract(NMP4-CT-2006-033231)and the SFI SRC BioNanoInteract(07 SRC B1155)Centre for Nano-Vaccine,Copenhagen,Denmark,and the Swedish Research Council(VR).
文摘Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticles.
基金Supported by Swiss National Science Foundation Grants to Dr.Vuilleumier N No.310030_140736and to Dr.Montecucco F No.32003B_134963/1a grant from the Foundation"Gustave and Simone Prévot"to Dr.Montecucco F
文摘Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.
基金supported financially by the program"Support of Young Investigators"MIS No.5005458 that was co-financed by the Operational Program"Human Resources Development,Education and Lifelong Learning"and by the European Union(European Social Fund)and Greek national funds。
文摘Apolipoprotein A-Ⅱ(APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein(HDL)synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis, though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial. Here, we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity. C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus Ad GFP, and five days post-infection blood and tissue samples were isolated. APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities. No effects on cholesterol efflux from RAW 264.7 macrophages were observed. Molecular analyses in white adipose tissue(WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ. Finally, overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin. In summary, expression of APOA-Ⅱ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality, adipose tissue metabolism and glucose utilization, many of which are beneficial to health.
基金the traditional Chinese medicine(TCM)clinical research base contribution subject of the State Administration of TCM of China(JDZX2012039)special scientific research of Chinese Medicine Industry of the State Administration of TCM of China(201207001)
文摘Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.
文摘The serum apolipoprotein A- I (apo A-I) Concentrations in 39 patients with posthepatitis cirrhosis were reported to be 0.87±0.27 g/L lower than that of controls 1.15±0.14 g/L P【0.01. The, decrease of apo. A-I was correlated with the severityof impaired liver function. Apo A- I concentrations in serum correlated positively with decrease of serum albumin (r=0.503 P【 0.01) and negatively with serum bilirubin increase (r=- 0.508 P 【0.01) . The data indicate that decreasing of apo A- I concentration may be regarded as one of the reliable indices reflecting the degree of liver function impairment.
文摘Objective:To explore the association between lipoprotein and arteriosclerosis in hospitalized and outpatient populations in western Beijing.Methods:Patients enrolled in the outpatient department and hospitalization from January 2013 to December 2017 were selected and eventually 258 cases were included in the study according to strict enrollment and exclusion criteria. The data were true and reliable. Statistically, an independent sample t-test and correlation analysis method were used, and the receiver operating characteristic curve was plotted using the predicted values of apolipoprotein A1 and apolipoprotein B for arteriosclerosis by controlling confounding factors.Results: Correlation analysis showed that there was a significant correlation between apolipoprotein B (P=0.007, correlation coefficient: -0.203) and carotid-femoral pulse wave velocity. Apolipoprotein A1 and apolipoprotein B had a strong diagnostic value for arteriosclerosis in patients without coronary heart disease. Conclusions: There is a significant negative correlation between apolipoprotein B and carotid-pulse wave velocity in the unconflicted patients in this study. Apolipoprotein A1 and apolipoprotein B have diagnostic value for arteriosclerosis.
文摘Mice overexpressing the human apolipoprotein apo CIII are a model of dyslipidemia. They become hypertxiglyceridemic, hypercholesterolemic and have high blood levels of free fatty acids. Blood glucose is normal, but as the liver integrates lipid and carbohydrate metabolism, conditions of high inter-tissue circulation of energy substxates, such as fasting, may reveal hepatic alterations of glucose metabolism in these （CIII） mice. This hypothesis was explored by in situ liver perfusion in this investigation. The NTG （non-txansgenic） animals showed liver and muscle glycogen content changes compatible with the fed or fasted state. In contrast, glycogen in group CIII was much lower in the fed state. The liver glucose release in group CIII after overnight fasting and adrenaline-stimulated was lower than in group NTG. Total glucose production under gluconeogenic conditions was not different between groups NTG and CIII, but glucose production from alanine was decreased in group CIII. Therefore, dyslipidemia caused by overexpression of apoCIII in mice alters the liver glucose metabolism, particularly compromising glycogen synthesis and degradation. This profile might have adverse outcomes during metabolic challenges that are more severe than fasting.
基金supported by a Borden Scholars awardDuke Claude D.Pepper Older Americans Independence Center Pilot Award(P30AG028716)by the NIH/NIA(R01AG081393)。
文摘Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.
