血清miR-663、miR-126和miR-370对冠心病患者支架内再狭窄的预测价值

目的研究血清微小RNA(miRNA)中的miR-663、miR-126和miR-370在冠心病患者支架植入术后的表达情况,分析以上3种miRNA对支架内再狭窄(ISR)的预测价值。方法研究纳入175例冠心病支架植入术后并随访复查冠状动脉造影的患者,根据造影结果分为ISR组(n=66)和无ISR组(n=109)。分析比较两组患者的临床资料。收集所有患者的血清,通过实时荧光定量PCR检测血清miR-663、miR-126和miR-370的表达情况。应用统计学方法分析以上3个miRNA预测ISR的价值。结果 175例支架植入术后冠心病患者中发生ISR的共66例。ISR组吸烟率更高(P0.05);ISR组血糖、低密度脂蛋白胆固醇、高敏C反应蛋白(hs-CRP)水平均高于无ISR组(P0.01)。ISR组血清miR-663、miR-126表达量低于无ISR组,而miR-370表达量高于无ISR组(均P0.01)。Logistic回归分析表明,miR-663、miR-126表达水平与ISR发生相关,吸烟、hs-CRP是ISR的独立危险因素。受试者工作特征曲线结果表明,miR-663、miR-126和miR-370预测ISR的曲线下面积(AUC)分别为0.772、0.720和0.650;而miR-663联合miR-126预测ISR的AUC为0.909,优于单一miRNA的预测效能。结论冠心病支架植入术后ISR患者血清miR-663、miR-126表达下降,miR-370表达增加。miR-663、miR-126和miR-370可用于预测ISR的发生,miR-663联合miR-126可明显提高预测ISR的效能。     

微小RNA-1在心血管疾病中的研究进展及作用机制

正微小RNA(microRNA,miRNA)是一类保守的单链非编码RNA分子,以序列特异性方式在转录后水平调控靶基因表达[1]。目前研究发现,动植物和病毒中均存在大量的miRNA表达,并可参与包括细胞增殖、凋亡、分化和代谢等多种生物学进程[2]。Bruno等[3]发现,miRNA在心血管疾病的发生发展过程中起重要作用。近年来,miRNA在心律失常,心力衰竭等疾病的研究中取得了一系列重要进展,使其成为国际心血管研究领域的热点,并已成为临床心血管疾病治疗的一个新的分子靶点。miR-1是近年来受关注的miRNA之一,其与心肌肥大、心律失常、心力衰竭及高血压等密切相关。     

微小RNA-27与心血管疾病

微小RNA(miRNA)对心血管疾病的发生发展起重要的调控作用。miR-27可以通过调节多种靶基因的表达直接或间接作用于心血管疾病的发生发展过程,该文就miR-27在心血管疾病中的调控作用机制作一综述。     

糖代谢异常对冠心病相关血清微小RNA表达的影响

目的检测相关血清微小RNA(miRNA)在冠心病及糖尿病合并冠心病患者中的表达水平,探讨糖代谢异常对冠心病相关血清miR-126、miR-146表达的影响。方法选择患者48例,分别为对照组15例,冠心病组17例,糖尿病合并冠心病组(合并组)16例。采用TaqMan探针实时定量PCR技术,检测各组血清miR-126、miR-146;采用TaqMan实时荧光定量PCR对血清中靶miRNA丰度进行定量。结果与对照组比较,冠心病组及合并组患者miR-126基因表达明显上调(P<0.05),而miR-146基因表达虽有下调趋势,但差异无统计学意义(P>0.05)。Spearman相关分析显示,CT miR-126与空腹血糖、餐后2h血糖水平呈负相关(r=-0.686,P=0.002;r=-0.723,P=0.001)。结论糖代谢异常对冠心病相关血清miR-126的表达产生影响,从而在一定程度上为miR-126成为糖尿病大血管病变的血清学检测指标提供理论依据。     

微小RNA对内皮细胞炎性反应过程中血管内皮细胞黏附分子1表达的影响

目的研究微小RNA(miRNA,miR-126)及血管细胞黏附分子1(VCAM-1)在脂多糖刺激的人脐静脉内皮细胞(HUVEC)中的表达,探讨miR-126对内皮细胞炎性反应过程中VCAM-1表达的影响。方法 HUVEC培养后分6组,空白对照组,模型组,miR-126mimic组,miR-126inhibitor组,A组和B组,后4组用Lipofectamine 2000脂质体分别转染miR-126mimic、miR-126inhibitor及miRNA mimics control、miRNA inhibitor control 24h后,加脂多糖1μg/ml刺激,在8h时,用实时荧光定量PCR检测miR-126、VCAM-1 mRNA表达;Western blot法测VCAM-1蛋白表达,并进行比较。结果模型组miR-126mRNA较空白对照组降低,为(0.056±0.004)倍(P0.01),而VCAM-1mRNA较空白对照组升高(12.50±2.55)倍(P0.01),VCAM-1蛋白表达明显升高(P0.01)。miR-126mimic组miR-126mRNA相对表达较A组升高(51.18±2.30)倍(P0.01),VCAM-1mRNA相对表达为A组(0.81±0.04)倍(P0.01),VCAM-1蛋白表达较A组明显降低(P0.01);miR-126inhibitor组miR-126mRNA表达较B组降低(0.032±0.011)倍(P0.01),VCAM-1mRNA水平较B组高(1.42±0.10)倍(P0.05),VCAM-1蛋白表达较B组明显升高(P0.05)。结论过表达miR-126在8h时下调VCAM-1的表达,提示miR-126可能通过抑制VCAM-1的表达,参与抑制脂多糖诱导的HUVEC的炎性反应。     

脑梗死患者血micro RNA表达水平对预后的影响

目的 探讨脑梗死患者血micro RNA(miRNA)表达水平对预后的影响。方法 选取邯郸市中心医院和安国市医院收治的63例急性脑梗死患者临床资料,分为两组,预后良好组31例,预后不良组32例。收集患者的一般资料,采集患者治疗前外周静脉血予以实时荧光定量-聚合酶链式反应(qPCR)检测miR-124、miR-125b、miR-126、miR-223、miR-422、miR-221、miR-335等miRNA的表达水平,进行多因素Logistic回归分析预后的影响因素。结果 两组患者吸烟、NIHSS评分之间差异有统计学意义(χ2/t=7.746、16.387,P 0.05)。预后良好组的miR-124、miR-125b、miR-126、miR-422、miR-221、miR-335水平显著低于预后不良组,而miR-223显著高于预后不良组,差异有统计学意义(t=8.421、6.348、5.434、9.847、7.987、10.346、7.652,P 0.05);miR-124、miR-125b、miR-126、miR-422、miR-221、miR-335、NIHSS评分均是影响不同预后的因素[OR(95%CI)=8.303(1.226～2.375)、4.241(1.119～6.890)、4.953(1.106～2.421)、4.860(0.316～5.900)、4.746(1.110～7.033)、6.677(0.266～8.219)、1.496(1.009～2.219),P 0.05)]。结论不同预后的脑梗死患者外周血miRNA表达水平存在差异,对患者miR-124、miR-125b、miR-126、miR-422、mi R-221、miR-335等指标进行监测,有助于观察患者的临床疗效及预后。     

miR-17-92基因簇在心血管疾病中的作用

我国心血管疾病负担沉重，严重威胁着人们的身心健康。研究证实，微小RNA(miRNA)在心血管疾病演变过程中扮演着重要角色。部分miRNA具有成簇聚集在染色体上的特点，其中miR-17-92基因簇是目前研究最为广泛的基因簇。本文归纳了近年来miR-17-92基因簇在心血管疾病中作用的相关研究，分析了miR-17-92基因簇各成员（miR-17、miR-18a、miR-19a、miR-19b、miR-20a、miR-92a）在动脉粥样硬化、心力衰竭、肺动脉高压、冠心病、心肌病病程进展中发挥的促进或抑制作用，并指出在今后的研究中需进一步明确miR-17-92基因簇各成员在心血管疾病中的相互协调作用机制，以便为临床治疗提供新靶点与新思路。     

微小RNA与缺血性心脏病的发生及治疗

微小RNA(miRNA)是近年来发现的一类长约22个核苷酸的内源性非编码RNA,通过与靶基因mRNA互补配对,介导转录后基因调控,在细胞的分化、增生、凋亡、个体发育以及机体代谢中都具有重要作用。新近研究发现,miRNA在缺血性心脏病形成过程中起着重要的基因调控作用:miR-29在心肌梗死后作为心肌纤维化的调节因素;miR-1与心肌纤维化有关,在心肌梗死后更易致心律失常;miR-21在血管成形术后再狭窄中起着重要作用;miR-126能增强血管生成作用;miR-133能刺激心肌的形成等等。因此,miRNA作为缺血性心脏病的检测指标和治疗工具也越来越受到关注,并可能成为治疗的新靶点。     

循环微小RNA识别冠状动脉粥样硬化不稳定斑块的价值研究

目的:探讨循环微小RNA(miRNA)对冠状动脉粥样硬化斑块特征的识别价值。方法:入选的120例急性冠脉综合征(ACS)患者,按斑块特点分为钙化斑块组(n=65)、非钙化斑块组(n=55),另选取同期60名健康体检者作为正常组。采集3组空腹静脉血检测miRNA(miR-16、miR-126、miR-155、miR-21、miR-221、miR-222)的表达水平,采用受试者工作特征曲线进行分析并计算各种循环miRNA诊断非钙化斑块患者的曲线下面积(AUC)。结果:非钙化斑块组、钙化斑块组及正常组的miR-16、miR-126、miR-155、miR-21、miR-221表达水平差异均具有统计学意义,非钙化斑块组的miR-21水平显著低于钙化斑块组和正常组;非钙化斑块组的miR-16水平显著高于钙化斑块组和正常组,差异均具有统计学意义(P均0.05);循环miRNA诊断非钙化斑块均具有一定的价值,miR-16+miR-21联合应用可以显著提高AUC。结论:外周血miR-16、miR-21水平表达与ACS患者的冠状动脉不稳定性斑块有关,可以作为判定斑块性质的诊断指标之一。     

同型半胱氨酸调控miRNA在心血管疾病中的作用研究进展

同型半胱氨酸(Hcy)是由蛋氨酸代谢生成的中间代谢产物,大量研究发现Hcy与心血管疾病有很大关系。微小RNA(miRNA)是一大类短链非编码RNA,已在多种疾病中证实miRNA失调可导致疾病的发生发展,比如免疫紊乱、糖尿病、癫痫、癌症等。目前miRNA因其在心血管系统中的关键作用而被认为是心血管疾病的新治疗策略。当前研究已证实Hcy与miRNA均是心血管疾病的危险因素,Hcy可通过调控miRNA影响心血管疾病,miRNA也可能对Hcy引起相应变化。但Hcy与miRNA的相互影响在心血管疾病中的作用还有待明确。本文简要综述了Hcy调控miRNA在心血管疾病中的作用进展及其潜在的临床应用价值。     

microRNA与心脏干细胞治疗

随着心血管病发病率的逐年增高,心脏干细胞(CSCs)治疗心血管病的研究已成为新的潮流。现已证实,microRNA(miRNA)是心血管的发育、病理生理过程和疾病发生中一类重要的调节因子。人们对心脏特异性miRNAs的研究已取得一定进展,如miR-1、miR-133、miR-208、miR-21、miR-499、miR-155、miR-146b及miR-126等在与CSCs协同治疗心血管病中起着不可或缺的作用。在此,本文对miRNAs在CSCs治疗中所起的作用做一综述。     

miR-223在心血管疾病中的研究进展

心血管疾病（cardiovascular disease，CVD）是目前危害人类生命健康的最重要的疾病，其中以冠心病（coronray heart disease, CHD）为甚。微小RNA(microRNA、miRNA）是一类在转录后水平调控基因表达及功能的小分子非编码RNA，参与多种疾病的病理生理过程。微小RNA-223（miR-223）是一种髓系特异性miRNA，在血小板、血浆、内皮细胞中含量丰富，可通过调控血小板及内皮细胞的多种基因表达及功能，参与CVD发生发展，如动脉粥样硬化、血栓形成，心肌代谢，血管生成等多个环节。本文就miR-223在CVD中的作用做一综述。     

MicroRNA-21 in Cardiovascular Disease

MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. miR-21 might be a novel therapeutic target in cardiovascular diseases. This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease.     

MicroRNA-126 is a regulator of platelet-supported thrombin generation

Abstract

Circulating microRNA (miRNA) expression profiles correlate with platelet reactivity. MiR-126 is a promising candidates in this regard. We generated a transgenic zebrafish line with thrombocyte-specific overexpression of miR-126. Laser injury of the posterior cardinal vein of 5 day-old larvae was performed with or without antithrombotic pre-treatment. Platelet-like structures (PLS) derived from human megakaryocytes transfected with miR-126 were also evaluated for procoagulant activity. Finally, we studied the correlation between miR-126 level and thrombin generation markers in a cohort of stable cardiovascular patients. Control zebrafish developed small thrombocyte-rich thrombi at the site of vessel injury, without vessel occlusion. The miR-126 transgenic line developed an occluding thrombus in 75% (95% CI: 51–91%) of larvae. Pre-treatment with the direct thrombin inhibitor argatroban, but not aspirin, prevented vessel occlusion in the transgenic line (0% occlusion, 95%CI: 0–18%). Upon activation, human PLS showed an increased procoagulant profile after miR-126 transfection compared to control. Finally, the plasma levels of miR-126, but not a control platelet-derived miRNA, correlated with markers of in vivo thrombin generation in a cohort of 185 cardiovascular patients. Our results from three complementary approaches support a key role for miR-126 in platelet-supported thrombin generation and open new avenues in the tailoring of antithrombotic treatment.     

Expression of miR-126 and miR-508-5p in endothelial progenitor cells is associated with the prognosis of chronic heart failure patients

Background

MicroRNA (miRNA) expression profiles in endothelial progenitor cells (EPCs) contribute to EPC dysfunction in patients suffering from coronary artery disease. However, it remains unclear whether miRNA expression in EPCs is associated with the prognosis of chronic heart failure (CHF) secondary to ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM).

Methods and results

One hundred six patients with CHF (55 ICM and 51 NICM) and 30 healthy controls were followed until the end of 24 months or when the end point was obtained (cardiovascular death). The miRNA expression profile was analyzed by TaqMan Human MicroRNA Array Set v2.0 in 30 randomly assigned samples (ICM = 10, NICM = 10, and healthy controls = 10). During the 24-month follow-up, 26 patients died from cardiovascular disease. Sixteen miRNAs (miR-126, miR-508-5p, miR-34a, miR-210, miR-490-3p, miR-513-5p, miR-517c, miR-518e, miR-589, miR-220c, miR-200a*, miR-186*, miR-7i*, miR-200b*, miR-595, and miR-662) were found to be differentially expressed between ICM and NICM patients. Survival analysis showed that miR-126 and miR-508-5p levels in EPCs were independent prognostic factors (P = 0.003; HR (hazard ratio): 0.19; 95% CI (confidence intervals): 0.06–0.58, P = 0.002; HR: 2.292; 95% CI: 1.37–3.84) for the outcome of ICM or NICM patients with CHF. Pathway enrichment analysis showed that the angiogenesis pathway was the most likely pathway regulated by miR-126 and miR-508-5p.

Conclusions

The miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF.     

miRNA在胆固醇逆向转运中的作用研究进展

胆固醇逆向转运(RCT)是体内清除胆固醇的唯一机制,对维持体内胆固醇稳态具有积极意义。miRNA是具有转录后调节基因表达能力的非编码RNA。现已在人体中鉴定出数百种miRNA,它们几乎参与所有过程的调节,包括胆固醇转运、新陈代谢和维持胆固醇稳态。由于它们的尺寸较小,并且能够特异性调节基因表达,因此miRNA逐渐成为调节血脂异常和其他脂质相关疾病的靶标。本文概述了可调节RCT的miRNA,主要包括miR-33、miR-19b、miR-144-3p、miR-223、miR-378等,重点介绍这些miRNA调节胆固醇代谢的机制,为防治动脉粥样硬化提供新思路。     

miRNA与COPD关系的研究进展

近年来,国内外的一些专家、学者发现一类非编码RNA尤其是miRNA,与呼吸系统疾病、心血管系统疾病、肿瘤等多种疾病的发生、发展相关,且认为其可作为某些疾病诊断、治疗、预后等生物标记物,为某些疾病的研究提供了新的切入点.本文主要就miRNA与COPD关系的研究进展作一综述.     

MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction

MicroRNAs (miRNAs) are important regulators of adaptive and maladaptive responses in cardiovascular diseases and hence are considered to be potential therapeutical targets. However, their role as novel biomarkers for the diagnosis of cardiovascular diseases still needs to be systematically evaluated. We assessed here for the first time whole-genome miRNA expression in peripheral total blood samples of patients with acute myocardial infarction (AMI). We identified 121 miRNAs, which are significantly dysregulated in AMI patients in comparison to healthy controls. Among these, miR-1291 and miR-663b show the highest sensitivity and specificity for the discrimination of cases from controls. Using a novel self-learning pattern recognition algorithm, we identified a unique signature of 20 miRNAs that predicts AMI with even higher power (specificity 96%, sensitivity 90%, and accuracy 93%). In addition, we show that miR-30c and miR-145 levels correlate with infarct sizes estimated by Troponin T release. The here presented study shows that single miRNAs and especially miRNA signatures derived from peripheral blood, could be valuable novel biomarkers for cardiovascular diseases.