微小RNA在心血管领域的研究进展

微小RNA是一种参与生长发育、器官形成、造血、细胞增殖与凋亡、肿瘤生成等多种生物学过程的重要调控因子,其作用机制主要是与靶信使RNA(mRNA)结合,进而抑制mRNA编码蛋白质的翻译或直接进行mRNA的切割.最近的一些研究发现,miRNAs不但参与了骨骼肌和心肌生长发育的调控,而且还参与了心脏的机械重构和电重构过程,并在调节血管内皮功能方面亦发挥着重要作用.以上发现使微小RNA有可能成为心血管界的一个新的治疗靶目标.     

微小RNA-缺血性心脏病治疗新的靶点

当前,缺血性心脏病（IHD）是世界主要死亡原因之一。IHD是指因冠状动脉不同程度的受阻引起冠状血流和心肌耗氧需求之间不平衡而导致的心肌损害,最终形成充血性心力衰竭。心脏缺血损伤后,非缺血部位的心肌出现心肌重构,如心肌间质纤维化和心肌肥厚。心肌的重构过程可使心脏功能进一步恶化,更容易诱发心律失常。微小RNA(microRNAs,miRNAs)是一类长约22个核苷酸的非编码小分子RNA,通过与靶蛋白 mRNA 3′端非编码区的不完全互补结合,抑制靶 mRNA 转录后的表达。最近大量研究显示,miRNA 在心脏病理、生理过程中发挥着重要的调控作用,尤其与心肌梗死和梗死后心脏重构的发生、发展密切相关。本文将从miRNAs在IHD中的调控作用进行阐述,并探讨以miRNAs为靶点改善IHD患者的临床转归。     

微小核糖核酸在缺血性心脏病中的研究进展

微小核糖核酸是一类参与生长发育、肿瘤发生、器官形成等生物学过程的重要调控因子。近期研究发现,微小核糖核酸与缺血性心脏病有重要关联,调节缺血或梗死后心肌纤维化、心律失常发生、血管成形术后再狭窄、新生血管形成以及心肌再生,影响心脏的机械重构、电重构及血管重构。以上发现使得微小核糖核酸有望成为缺血性心脏病新的治疗靶点。     

基质金属蛋白酶与充血性心力衰竭时心脏重构

充血性心力衰竭(CHF)发展过程中,心脏发生几何形状和心肌结构的改变称为心脏重构。过去曾认为心脏重构只是由于心肌细胞内源性的变化,现在认识到心肌细胞外基质(ECM)中胶原的数量、组成和结构的变化也参与了心脏重构过程〔1〕。基质金属蛋白酶(MMPs)是一组特异地降解ECM成分、参与心脏重构的酶家族。在人体与动物CHF的心肌组织中都可以发现MMPs表达〔1～4〕。MMPs是心肌间质重构中基质降解的推动力量。通过调控MMPs的表达与活性,可以影响ECM的数量、组成和结构,可能成为阻止甚至逆转心力衰竭(心衰)时心脏重构新的治疗途径。1 　…     

心脏交感神经重构与心律失常的关系

心脏内广泛分布着交感神经并受其支配,交感神经在调节心率、心脏传导、心肌收缩和舒张等方面发挥了重要作用。近年研究发现,在很多心脏疾病中,交感神经的分布、密度、功能都发生了不同程度的改变。即我们所述的交感神经重构。心律失常在临床很常见,长期以来对心律失常的电生理机制的研究比较多,而近几年很多学者研究发现在心脏疾病中伴有的心脏交感神经重构与心律失常的发生有着密切的关联。心脏交感神经重构与心肌组织重构、电重构的相互影响可能是心律失常发生的基础。对交感神经重构进行药物与非药物干预可能是控制心律失常发生的一个新的治疗途径。     

MicroRNAs作为大肠癌生物标志物的研究进展

MicroRNAs(miRNAs)是一种短链(19-24个核苷酸)非编码RNA,可抑制蛋白质翻译或其靶基因mRNAs的降解,因而在基因表达调控中发挥重要作用.最近的研究发现存在于大肠癌(colorectal cancer,CRC)组织和血液中的miRNAs可较准确地诊断大肠癌的存在,并帮助判断CRC临床病理特征及预测疾病复发,特异miRNAs的过表达和沉默与CRC的发生发展相关,且其在CRC组织和血液中的差异表达为早期筛选和诊断CRC提供了应用前景.另外,miRNAs可能成为CRC基因治疗的重要靶点.本文将就miRNAs作为生物标志物在CRC诊治中的潜在作用作一综述.     

microRNAs在心肌梗死中的研究进展

microRNAs(miRNAs)是一种非编码小分子RNA,通过降解mRNA或阻碍其翻译调控基因的表达。心肌梗死是一种常见的心血管疾病,导致心脏重构,最终发展为心力衰竭。miRNAs在心肌梗死的病理生理发展过程中起着重要作用,其可以促进或抑制心肌细胞凋亡,调控心肌细胞增,调节血管再生,此外还能调控心脏成纤维细胞重编程为心肌细胞。本文将综述miRNAs在心肌梗死中的最新进展和治疗前景。     

microRNAs在心肌肥厚中的作用

生理或病理性刺激会导致心肌肥厚性生长,表现为心肌细胞增大,蛋白合成增加及胎儿基因的再表达。在心脏中有很多信号分子影响着基因表达、细胞凋亡、细胞因子释放等病理生理过程。利用心肌细胞肥厚模型已经发现病理性心肌肥厚可以被抑制或逆转,这些发现为寻找调控心肌肥厚的因子及信号通路提供了基础。该文着重讨论近年来发现的microRNAs(miRNAs)在调节心肌肥厚中的作用。     

微小RNA与心肌纤维化关系的研究进展

心肌纤维化是临床上多种心脏疾病共同经历的一种病理过程,对心脏细胞重构、心脏的电传导、心功能等都有很大的影响。微小RNA是一类由16~22个核苷酸分子组成的单链非编码核糖核酸片段,以调控基因表达的方式参与各种生理和病理过程。在心肌纤维化的病理发展过程里,很多种微小RNA被发现参与其中,并且在心肌纤维化过程中扮演重要的角色,有的起到促进心肌纤维化作用,有的则有抑制心肌纤维化的心肌保护作用。研究这些微小RNA和心肌纤维化之间的关系,可丰富临床对心肌纤维化的诊疗思路和途径。现对近年研究发现的一部分参与调节心肌纤维化的微小RNA做一综述。     

HBV/HCV相关miRNAs研究进展

microRNAs（miRNAs）是一类由约22个核苷酸组成的非编码单链RNAs,通过抑制蛋白质翻译或降解mRNAs调节基因的表达。目前发现有2000多种人源miRNAs,参与调节发育、细胞增殖、凋亡以及压力反应过程中的基因表达等,而miRNAs基因突变或者异常表达可能会引发肿瘤等疾病。已有研究表明miRNAs在肝炎病毒（HBV、HCV等）感染以及肝癌的发生发展过程中,也发挥了重要的作用。本文主要就HBV/HCV调控宿主miRNAs,以及miRNAs如何影响病毒的复制等方面进行阐述。     

miRNAs as Therapeutic Targets in Ischemic Heart Disease

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.     

A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure

Diverse forms of injury and stress evoke a hypertrophic growth response in adult cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, assembly of sarcomeres, and reactivation of fetal genes, often culminating in heart failure and sudden death. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we searched for miRNAs that were regulated during cardiac hypertrophy and heart failure. We describe >12 miRNAs that are up- or down-regulated in cardiac tissue from mice in response to transverse aortic constriction or expression of activated calcineurin, stimuli that induce pathological cardiac remodeling. Many of these miRNAs were similarly regulated in failing human hearts. Forced overexpression of stress-inducible miRNAs was sufficient to induce hypertrophy in cultured cardiomyocytes. Similarly, cardiac overexpression of miR-195, which was up-regulated during cardiac hypertrophy, resulted in pathological cardiac growth and heart failure in transgenic mice. These findings reveal an important role for specific miRNAs in the control of hypertrophic growth and chamber remodeling of the heart in response to pathological signaling and point to miRNAs as potential therapeutic targets in heart disease.     

miRNome in myocardial infarction: Future directions and perspective

MicroRNAs(miRNAs), which are small and non-coding RNAs, are genome encoded from viruses to humans. They contribute to various developmental, physiological and pathological processes in living organisms. A huge amount of research results revealed that miRNAs regulate these processes also in the heart. miRNAs may have cell-type-specific or tissue-specific expression patterns or may be expressed ubiquitously. Primary studies of miRNA involvement in hypertrophy, heart failure and myocardial infarction analyzed miRNAs that are enriched in or specific for cardiomyocytes; however, growing evidence suggest that other miRNAs, not cardiac or muscle-specific, play a significant role in cardiovascular disease. Abnormal miRNA regulation has been shown to be involved in cardiac diseases, suggesting that miRNAs might affect cardiac structure and function. In this review, we focus on miRNAs that have been found to contribute to the pathogenesis of myocardial infarction(MI) and the response post-MI and characterized as diagnostic, prognostic and therapeutic targets. The majority of these studies were performed using mouse and rat models of MI, with a focus on the identification of basic cellular and molecular pathways involved in MI and in the response post-MI. Much research has also been performed on human and animal plasma samples from MI patients to identify miRNAs that are possible prognostic and/or diagnostic targets of MI and other MI-related diseases. A large proportion of research is focused on miRNAs as promising therapeutic targets and biomarkers of drug responses and/or stem cell treatment approaches. However, only a few studies have described miRNA expression in human heart tissue following MI.     

Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis

Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied by a pathological remodeling response that includes hypertrophic cardiac growth and fibrosis, which impair cardiac contractility. Previously, we showed that cardiac hypertrophy and heart failure are accompanied by characteristic changes in the expression of a collection of specific microRNAs (miRNAs), which act as negative regulators of gene expression. Here, we show that MI in mice and humans also results in the dysregulation of specific miRNAs, which are similar to but distinct from those involved in hypertrophy and heart failure. Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.     

NADPH氧化酶亚基在心脏重构中作用的比较

早期研究证实,烟酰胺腺嘌呤二核苷酸(还原型辅酶Ⅱ,NADPH)氧化酶在血管紧张素Ⅱ(AngⅡ)介导的心室重构中发挥重要作用,随着对NADPH氧化酶的深入研究,发现其共有5种亚基和两种相关的亚基,其中在心脏组织中表达的主要为Nox2与Nox4。Nox2在AngⅡ、心肌梗死及阿霉素介导的心室重构中具有重要的促进作用,而在压力负荷过大时引起的左心室肥大中Nox4 mRNA表达上调明显,由此可得出NADPH氧化酶亚基Nox2与Nox4在心室重构中的作用不同。因此,深入研究NADPH氧化酶亚基及其在心室重构中的作用,将成为改善心室重构新的治疗靶点。     

心肌成纤维细胞的特性和调节

心肌成纤维细胞在心脏中是数量最大的细胞,它们通过维持细胞外基质平衡在受损或衰竭心脏中纤维化心肌重塑发挥重要作用。它既调节正常的心脏功能,也参与高血压病、心肌梗死和心力衰竭等的不良心肌重塑。综述心肌成纤维细胞的特性,包括起源、机械电特性、细胞外基质代谢中的作用,以及正常和病理状态下心肌成纤维细胞对环境刺激的功能反应和分泌生物活性因子的能力,并总结以心肌成纤维细胞为靶细胞调节心肌纤维化的研究现状。