microRNAs:心血管疾病重要的调控因子

微RNA（microRNA,miRNA）是一类内源性19—25个核苷酸大小的非编码RNA分子,在进化中具有高度保守性,并且能够通过碱基匹配原则识别靶基因3’非翻译区的靶位点,从而抑制编码蛋白靶基因的翻译或（和）降解靶基因。目前的研究表明,miRNA在生物体发育、心血管疾病以及肿瘤发生等过程中起重要作用。本文对miRNA在心血管系统生理病理中的作用做一综述。     

去甲基化酶FTO在心血管疾病中的研究进展

脂肪和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)是N6-甲基腺苷(m6A)调控系统中关键的去甲基化酶.既往研究发现,FTO可参与肥胖、糖尿病以及昼夜节律等增加心血管疾病的患病和发病风险.FTO在心肌梗死、心肌肥厚以及心力衰竭的发生发展中均具有重要调控作用,可能...     

内皮-间质转化与心血管疾病的研究进展

内皮-间质转化(endothelial-to-mesenchymal transition,End MT)属于上皮-间质转化(epithelial-to-mesenchymal transition,EMT)的特殊类型,是内皮细胞在多种刺激因素作用下向间充质细胞转化的过程,在此过程中内皮细胞逐渐失去其形态和功能,获得增殖、迁移和合成胶原等间充质细胞表型特点.近来研究发现,内皮-间质转化在内皮功能调节,心肌、血管及瓣膜的发育和结构重塑等方面发挥着关键的作用,提示其在心血管疾病领域具有重要的研究意义.本文对内皮-间质转化的特点、功能、调节机制以及在心血管系统发育、心肌纤维化、肺动脉高压和动脉粥样硬化性血管重构等心血管疾病中的作用做一综述,以期为心血管疾病的防治提供新靶点.     

抑制心肌纤维化促进心肌再生治疗慢性心血管疾病

以心肌肥厚、心肌细胞丢失和心肌组织纤维化为特征的心脏组织异常重构是各种慢性心血管疾病的核心病理改变。以组织异常重构,特别是以组织纤维化为靶点,利用小分子化合物如松弛素、KNK437,生物制剂如BCG、抗TLR2抗体或中药复方CFX等改变炎症性质,抑制甚至逆转纤维化不仅可以有效地改善心脏功能,还可为干细胞的动员和生长提供适宜环境,促进心肌再生,是治疗慢性心血管疾病的重要途径。     

生长分化因子-15在肥胖、糖尿病及心血管疾病中的作用

生长分化因子-15(growth differentiation factor-15,GDF-15),又称巨噬细胞抑制因子-1,是转化生长因子-β(transforming growth factor-β,TGF-β)家族的一个应激反应细胞因子,在产前发育、炎症、应激反应以及急性损伤后的组织修复中起关键作用.GDF-1...     

脂联素与心血管疾病

脂联素是由脂肪组织分泌的一种细胞因子,与心血管疾病密切相关。脂联素通过抗炎和抗氧化抑制动脉粥样硬化发生。脂联素可促进血管生成,并具有保护心肌免受缺血再灌注损伤和减轻高压力负荷导致的心肌肥厚的功能。脂联素主要通过激活腺苷酸活化的蛋白激酶、环磷酸腺苷-蛋白激酶A等信号通路而发挥对心血管的保护作用。该文主要针对脂联素在心血管系统中的作用及其分子机制的研究进展作一综述。     

阿司匹林对大鼠心梗后心肌纤维化演进的干预效果

目的：初步探讨阿司匹林对心梗后心肌纤维化的干预效果。方法：通过结扎大鼠左冠状动脉建立心梗模型,依随机化原则从模型组选出大鼠作为阿司匹林组（1mL/100g/d）,其余入选模型组。4周后检测两组血流动力学相关参数,处死大鼠取出心脏并记录心肌纤维化相关参数。结果：4周后阿司匹林组与模型组相比,其血流动力学参数和心肌纤维化参数均有显著差异（LVSP：t=18.323,P=0.000;LVDP;t=11.516,P=0.000;LVMP：t=10.767,P=0.000;LVD;t=11.736,P=0.000;LVAW：t=8.734,P=0.000）,可不同程度改善心肌机械功能,预防和推迟心肌纤维化发生。结论：阿司匹林可一定程度预防和推迟梗死后心肌纤维化演变进程。     

microRNAs在大鼠急性心肌梗死过程的表达变化

目的研究分析microRNAs（miRNAs,miRs）在大鼠急性心肌梗死（acutemyocardialinfarction,AMI）心肌组织的梗死区与非梗死区的表达变化,为防治AMI提供基础数据。方法选择雄性sD大鼠为研究对象,建立结扎左冠状动脉造成的急性心肌梗死模型,取建模后6h的梗死区与非梗死区的心肌组织进行芯片检测．确定其中表达变化显著的miRNAs;最后进行定量逆转录聚合酶链反应（qRT—PCR）,定量分析梗死区与非梗死区心肌组织中miRNAs的表达。结果AMI大鼠心肌组织中,芯片筛选出在AMI前后发生显著波动的miRNAs,与非梗死区相比,梗死区心肌组织中有26个miRNAs表达发生了显著变化,其中19个miRNA表达下调,7个miRNA表达上调。结论在AMI后的心肌组织的梗死部位与非梗死部位miRNAs的表达是有显著差异的,这对AMI阶段心肌保护的救治具有重要意义。     

缝隙连接与心血管疾病

缝隙连接(gap junction,GJ)是存在于相邻组织细胞间特殊的膜通道结构,相邻的细胞通过缝隙连接进行着信息的交流,能量和物质的交换。缝隙连接参与了细胞间电信号传递的电偶联和物质交换的代谢偶联,在细胞的内环境稳定、新陈代谢、增殖和分化等生理过程起着重要的作用。缝隙连接表达、分布重构、结构和功能的改变均能影响缝隙连接的功能,导致多种心血管疾病的发生。本文就近年来缝隙连接在心血管疾病发生中作用的研究现状作一综述。     

Sirtuin6在心血管疾病中的作用

衰老是心血管疾病发生发展的独立危险因素,Sirtuin蛋白家族(SIRT1-7)是一组与衰老和寿命密切相关的烟酰胺腺嘌呤二核苷酸(NAD~+)依赖性组蛋白去乙酰化酶,在饮食限制和运动等情况下可被激活,以维持代谢稳态,保护心血管疾病。SIRT6作为该家族相对新成员,可参与多种基因表达、DNA损伤修复等过程的调控,被认为是一种肿瘤抑制因子和促进长寿的正向调节因子,但其在心血管疾病中的作用尚未被完全揭示。近年来,有研究显示SIRT6可延缓与年龄相关的心血管疾病进程,具有发展为心血管疾病治疗靶点的潜力。本文现就SIRT6在心血管疾病中作用的研究进展进行综述。     

Role of non-coding variants in cardiovascular disease

Cardiovascular diseases (CVDs) constitute one of the significant causes of death worldwide. Different pathological states are linked to CVDs, which despite interventions and treatments, still have poor prognoses. The genetic component, as a beneficial tool in the risk stratification of CVD development, plays a role in the pathogenesis of this group of diseases. The emergence of genome-wide association studies (GWAS) have led to the identification of non-coding parts associated with cardiovascular traits and disorders. Variants located in functional non-coding regions, including promoters/enhancers, introns, miRNAs and 5′/3′ UTRs, account for 90% of all identified single-nucleotide polymorphisms associated with CVDs. Here, for the first time, we conducted a comprehensive review on the reported non-coding variants for different CVDs, including hypercholesterolemia, cardiomyopathies, congenital heart diseases, thoracic aortic aneurysms/dissections and coronary artery diseases. Additionally, we present the most commonly reported genes involved in each CVD. In total, 1469 non-coding variants constitute most reports on familial hypercholesterolemia, hypertrophic cardiomyopathy and dilated cardiomyopathy. The application and identification of non-coding variants are beneficial for the genetic diagnosis and better therapeutic management of CVDs.     

同型半胱氨酸在心血管疾病中的免疫调节作用

高同型半胱氨酸血症是动脉粥样硬化的独立危险因子,但是其致病机制尚未完全阐明。本文将从体液免疫、单核巨噬细胞以及T细胞活性等几方面归纳总结同型半胱氨酸在心血管疾病中的免疫调节作用。同型半胱氨酸可以诱导单核细胞和T细胞分泌趋化因子和细胞因子,还可以直接刺激B细胞增殖及IgG分泌。此外,本文还总结了高同型半胱氨酸致炎作用的细胞内机制。同型半胱氨酸可以直接或间接导致氧化应激或者内质网应激,还可以降低一氧化氮的生物活性,影响包括S-腺苷蛋氨酸和S-腺苷同型半胱氨酸的水平,从而导致心血管疾病的发生。     

Conventional and novel diagnostic biomarkers of acute myocardial infarction: a promising role for circulating microRNAs

Abstract

Biomarkers play a critical role in the diagnosis of acute myocardial infarction (AMI), especially in patients with atypical clinical and/or electrocardiographic presentation or co-morbidities, like the elderly. High-sensitivity assays based on specific biomarkers (e.g. cardiac troponins) enabling earlier AMI diagnosis have recently become available in clinical practice. Although no single biomarker of myocardial necrosis is ever likely to afford AMI diagnosis, a combination including different biomarkers for necrosis and ischemia, like new circulating molecules (microRNAs), could enhance diagnostic specificity. We review the recent literature on conventional and novel AMI biomarkers, with special emphasis on circulating microRNAs.     

Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post‐myocardial infarction rats

Danqi soft capsule (DQ) is a traditional Chinese medicine containing Salvia miltiorrhiza and Panax notoginseng; it is safe and efficient in treating ischaemic heart diseases. The purpose of the present study was to assess whether DQ could prevent infarct border zone (IBZ) remodelling and decrease ventricular arrhythmias occurrence in post‐myocardial infarction (MI) stage. MI was induced by a ligation of the left anterior descending coronary artery. DQ was administered to the post‐MI rats started from 1 week after MI surgery for 4 weeks. The results showed that DQ treatment significantly attenuated tachyarrhythmia induction rates and arrhythmia score in post‐MI rats. In echocardiography, DQ improved left ventricular (LV) systolic and diastolic function. Histological assessment revealed that DQ significantly reduced fibrotic areas and myocyte areas, and increased connexin (Cx) 43 positive areas in IBZ. Western blot revealed that DQ treatment significantly reduced the protein expression levels of type I and III collagens, α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1) and Smad3 phosphorylation, while increasing Cx43 amounts. Overall, these findings mainly indicated that DQ intervention regulates interstitial fibrosis, Cx43 expression and myocyte hypertrophy by TGF‐β1/Smad3 pathway in IBZ, inhibits LV remodelling and reduces vulnerability to tachyarrhythmias after MI. This study presents a proof of concept for novel antiarrhythmic strategies in preventing IBZ remodelling, modifying the healed arrhythmogenic substrate and thus reducing susceptibility to ventricular arrhythmias in the late post‐MI period.     

线粒体融合蛋白2与心血管疾病

线粒体融合蛋白2(mitofusin2,Mfn2)不仅是一种不可或缺的调控线粒体形态和功能的动力素(dynamin)相关蛋白,还是一个重要的细胞内信号分子,参与调控细胞增殖、分化、凋亡等生命过程。Mfn2与高血压、冠状动脉腔内成形术后再狭窄、动脉粥样硬化、心肌肥厚、心肌氧化损伤等多种心血管疾病的病理生理过程密切相关,并通过调节物质代谢影响糖尿病和胰岛素抵抗等的发病。此外,Mfn2还可能是心血管疾病的一个重要的分子标志和治疗靶分子。     

Arrhythmogenic risks of stem cell replacement therapy for cardiovascular diseases

Ischemic heart disease and congestive heart failure are major contributors to high morbidity and mortality. Approximately 1.5 million cases of myocardial infarction occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. Although significant progress to improve the survival rate has been made by medications and implantable medical devices, damaged cardiomyocytes are unable to be recovered by current treatment strategies. After almost two decades of research, stem cell therapy has become a very promising approach to generate new cardiomyocytes and enhance the function of the heart. Along with clinical trials with stem cells conducted in cardiac regeneration, concerns regarding safety and potential risks have emerged. One of the contentious issues is the electrical dysfunctions of cardiomyocytes and cardiac arrhythmia after stem cell therapy. In this review, we focus on the cell sources currently used for stem cell therapy and discuss related arrhythmogenic risk.