miRNA与冠心病的研究进展

微小核糖核酸(microRNA,miRNA)是一类中高度保守的单链非编码小RNA,主要在转录后水平调控基因的表达。近年来许多研究表明miRNA在心血管系统中高度表达,与动脉粥样硬化、冠心病、心力衰竭、心律失常等心血管疾病密切相关。本文就miRNA与冠心病相关的研究进展作一综述。     

miRNA polymorphisms and risk of premature coronary artery disease

ObjectiveSeveral microRNA (miRNA) polymorphisms have been associated with susceptibility to specific health disorders, including cardiovascular diseases. The aim of the present study was to investigate whether four well-studied miRNA polymorphisms in non-Caucasian populations, namely miR146a G>C (rs2910164), miR149 C>T (rs2292832), miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), contribute to the risk for the development of premature Coronary Artery Disease (CAD) in the Greek population.MethodsWe used a case-control study to examine these associations in 400 individuals: 200 CAD patients [including a subgroup of myocardial infraction (MI) patients] and 200 healthy controls, all of Greek origin. MiRNA polymorphisms were genotyped using three different assays: Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), High resolution Melting (HRM) and Sanger sequencing.ResultsTwo of these polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444) were found to be strongly associated with increased risk for CAD (p=0.0388 and p=0.0013, respectively) and for MI (p=0.0281 and p=0.0273, respectively). Furthermore, miR146C-miR149C-miR196T-miR499G allele combination appeared to be significantly related to CAD (p=0.0185) and MI (p=0.0337) prevalence.ConclusionsOur results suggest that at least two of the studied polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), as well as the miR146C-miR149C-miR196T-miR499G allele combination could represent useful biomarkers of CAD and/or MI susceptibility in the Greek population. These special genetic characteristics, in combination with environmental factors and personal habits, might contribute to CAD and/or MI prevalence.     

冠心病新的危险因素

冠心病是目前全球范围最常见的心血管疾病 ,它的发生是由外界环境因素和内在的多基因调控异常共同作用的结果。已报道的冠心病危险因素有 2 0 0多种 ,包括我们已经熟悉的危险因素和一些新的危险因素。本文就冠心病的一些新的危险因素做一简述     

Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations?

OBJECTIVE: To investigate the relation between Helicobacter pylori infection and coronary heart disease (CHD). DESIGN: A case-control study. SETTING: Northern Finland (about 650,000 inhabitants). PATIENTS: 116 patients with angiographically documented CHD and 116 controls matched for age and gender randomly recruited from the register of the Finnish Social Insurance Institute. MAIN OUTCOME MEASURES: The odds ratio (OR) estimates for the association of H pylori infection with CHD. RESULTS: 64% of the CHD patients and 53% of the controls were seropositive for H pylori; the OR adjusted for age and gender was 1.5 (95% confidence interval (CI) 0.9 to 2.5). An additional adjustment for the common risk factors of CHD, including lipid concentrations, in a logistic regression analysis produced an OR estimate of 1.1 (95% CI 0.6 to 2.1). Among the controls, those who were H pylori positive had significantly (P = 0.03) higher concentrations of serum triglycerides than those who were H pylori negative: the trend among the cases was similar, but non-significant. The concentrations of HDL cholesterol tended to be lower in those who were H pylori positive than in those who were H pylori negative, among both the cases and the controls. CONCLUSIONS: The impact of H pylori infection as an independent risk factor for CHD seems to be minor. On the other hand the results are consistent with the hypothesis that H pylori infection might modify the serum lipid concentrations in a way that could increase the risk of CHD.     

冠心病患者血浆微小RNA作为生物标记物可能性的研究

目的探讨微小RNA(miRNA)在动脉粥样硬化性心脏病患者循环血浆中表达特点。方法选择男性冠心病患者32例作为冠心病组,男性健康体检者20例作为对照组。另选择载脂蛋白(apo)E-/-小鼠10只为实验组,正常C57BL/6J小鼠10只为观察组,用高通量基因芯片技术分析实验组和观察组小鼠血浆中差异表达的miRNA。用实时定量PCR法检测冠心病组和对照组miRNA的表达。结果与观察组比较,实验组小鼠血浆有14种miRNA显著差异表达,其中6种显著上调3.02~3.46倍,8种显著下调3.02~4.21倍。与对照组血浆miRNA表达比较,冠心病组miR-34a和miR-21显著上调、miR-23a显著下调(P<0.01)。结论冠心病患者循环血浆中miR-23a、miR-21、miR-34a较健康人群明显升高,提示这3种miRNA具有成为冠心病患者生物标记物的潜能。     

血清淀粉样蛋白A与冠心病及冠心病危险因素的关系

目的 :探讨血清淀粉样蛋白A (SAA)与冠心病 (CHD)及CHD相关危险因素的关系。方法 :用微粒增强免疫比浊法测定SAA的血浆浓度。结果 :急性冠状动脉综合征 (ACS)亚组和稳定型心绞痛 (SAP)亚组SAA血浆浓度均高于对照组 (P <0 .0 1) ;ACS亚组SAA血浆浓度高于SAP亚组 (P <0 .0 1) ;比较CHD危险因素导致CHD发生的危害性 ,SAA >CHD家族史 >TC >吸烟指数 >高血压史。结论 :CHD患者SAA血浆浓度升高可促进动脉粥样斑块的不稳定性 ,导致ACS的发生     

Women and coronary heart disease risk factors

The prevalence of cardiovascular risk factors among women is high and cardiovascular risk factors often occur in clusters. Strong relationships between exposure to cigarette smoke, physical inactivity, hypertension, and abnormal levels of lipoproteins and homocysteine and subsequent coronary heart disease (CHD) in women are evident from many studies, while the impact of menopause, psychosocial factors, and inflammatory markers is less clear and requires further study. Observational studies document that smoking cessation reduces CHD risk among persons with and without existing CHD, and that moderate levels of physical activity are associated with lower CHD risk. Clinical trials over the last decade have convincingly shown that treatment of hypertension and dyslipidemia reduces CHD risk in both genders, but many women (and men) with hypertension and dyslipidemia remain either untreated or under-treated.     

Hypertriglyceridemia and risk of coronary heart disease

Mounting evidence indicates that elevated triglyceride level is a risk factor for coronary heart disease (CHD). The role of triglyceride as a causative agent for CHD is less clear. Hyper-triglyceridemia is frequently associated with a set of complex metabolic abnormalities, including low high-density lipoprotein cholesterol, small dense low-density lipoprotein, central obesity, insulin resistance, and type 2 diabetes. Understanding the physiologic processes that lead to the metabolic disturbances associated with hypertriglyceridemia is essential in investigating the effect of triglyceride on CHD risk.     

冠心病患者亚甲基四氢叶酸还原酶基因多态性87例研究

目的探讨N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与冠心病的关系。方法对2003年11月至2005年8月贵阳医学院附属医院及贵州市第二人民医院住院的87例冠心病患者(冠心病组)及同期在门诊进行健康体检的73名健康人(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测其MTHFRC677T基因多态性。结果对照组与冠心病组MTHFR677位T等位基因的分布频率分别是18.5%,36.1%,病例组MTHFR基因C677T的CT基因型及T等位基因频率显著高于对照组,差异有显著性(P<0.05)。结论MTHFRC677T基因多态性与冠心病密切相关。     

Projected coronary heart disease risk benefit with ezetimibe

Low density lipoprotein (LDL) cholesterol and total cholesterol (TC) are the primary clinical parameters of interest for any cholesterol intervention. Clinicians are interested in how the reduction of these lipid parameters as well as increases in high density lipoprotein (HDL) relate to changes in coronary heart disease (CHD) risk. The objective of this analysis was to estimate the additional CHD risk reduction that could potentially be provided by co-administration of ezetimibe with statin therapy. Data from four double-blind placebo controlled clinical trials were used to predict the level of CHD risk reduction that might be achieved by co-administration of ezetimibe with statin therapy when compared to those receiving statin as monotherapy. Patients without a previous history of CHD were included in the analysis. Projected CHD risk reduction was calculated as percent change in projected CHD risk from baseline to 12 weeks based on observed lipid levels at those time points. For all the studies combined greater reductions in percent change in 5-year CHD risk were observed for patients receiving ezetimibe and statin as co-therapy, 53.4%, when compared to those receiving statin alone, 39.7%. Co-administration of ezetimibe with statin therapy provides an additional 13.7% reduction in predicted 5-year CHD risk when compared to statin monotherapy. Reductions in 5-year CHD risk for each of the statin studies ranged from 16.1% for lovastatin to 9.8% for atorvastatin. Co-administration of ezetimibe with statins could significantly reduce CHD events in patients with primary hypercholesterolemia.