miRNAs对血管平滑肌细胞功能的调节与心血管疾病

miRNA(miRNAs)是一类长约18～24个核苷酸的高度保守性的小分子非编码RNA,主要通过与特异性靶基因mRNA 3’-UTR区结合来调控基因的表达。miRNAs与细胞增殖、分化、凋亡、胚胎发育、组织器官等形成以及多种疾病的发生发展密切相关。新近研究显示,miRNAs对血管心血管平滑肌细胞功能及心血管疾病的发生发展起着重要的调节作用。本文就miRNAs对血管平滑肌细胞功能的调节及心血管疾病的病理生理学意义作一概述。     

microRNA转基因小鼠在心脏发育研究中的应用

microRNA（miRNA）参与调控胚胎心脏的发育,在心脏形态发生、心肌细胞生长及分化过程中发挥着极其重要的作用。通过转基因技术可以实现特异miRNA在心肌组织的过表达与敲除,据此建立的心肌特异性miRNA转基因小鼠模型可以在整体水平揭示miRNA心脏方面的功能。近年,以miRNA为研究对象的心肌特异性转基因小鼠模型数量不断增加。     

微核糖核酸对血管生成相关因子的调节作用

微核糖核酸(microRNAs,miRNAs)是广泛存在于真核生物中的一类短小的、非编码的单链RNA,由18～25个核苷酸组成,在调节细胞增殖、分化、凋亡和肿瘤发生等多种生物学过程中起重要作用.血管生成过程中受到多种血管生成因子的调控作用,近期研究表明,microRNAs参与血管生成相关因子的调节,进而影响血管生成,然而具体的功能以及作用机制仍需探讨.进一步研究microRNAs对血管生成相关因子的调控作用,为心血管疾病和肿瘤的治疗提供新的理论基础.     

EZH2在心脏与血管发育中的作用

Zeste基因增强子人类同源物2(enhancer of zeste homolog 2, EZH2)是多梳蛋白抑制复合物2(polycomb repressive complex 2, PRC2)的主要元件之一，利用组蛋白甲基化酶活性发挥经典作用，抑制靶基因的表达。此外，EZH2通过甲基化其他蛋白，作为蛋白支架分子募集转录相关分子介导转录激活，与lncRNA及miRNA相互作用等非经典途径调控各项生命活动，与干细胞分化和组织器官发育关系密切。EZH2及其功能相关分子在心脏发育、血管发生等过程中发挥着至关重要的作用。靶向敲除小鼠心脏Ezh2基因会影响心肌组织及内皮源性组织的正常发育，造成广泛性的心脏发育缺陷。EZH2参与调控正常组织和肿瘤组织的血管生成，维持新生血管完整性，并参与调控内皮间质化和内皮造血转化。本文探讨了EZH2在心脏和血管发生领域的影响效应、调控机制，及其与相关疾病的关系。     

MicroRNA与肿瘤血管生成

microRNA（miRNA）是近年来发现的一类长度约为22个核苷酸的非编码小分子RNA.它主要通过与靶标基因3′UTR的完全或不完全配对,降解靶标基因mRNA或抑制其翻译,从而参与多种生命活动.血管生成在肿瘤的发生、发展过程中起着重要的作用.实验证据表明,miRNAs可通过调控其靶标基因参与的信号通路,影响肿瘤血管的生成.本文主要介绍近年来miRNAs与血管生成相关性研究的进展.     

睾丸发育和精子生成相关miRNA研究进展

MicroRNA(miRNA)是一类长约22nt的非编码小RNA, 广泛存在于各种生物中, 调节生物体生长、发育和凋亡等过程。研究表明, miRNA在人和动物睾丸发育及精子生成等过程也起着重要的调控作用。但miRNA在不同种属的睾丸组织及其不同发育时间段均存在特异性表达。此外, miRNA在动物精子生成过程中也存在时空特异性。文章综述了睾丸发育和精子生成过程中miRNA的差异性表达、表达调控以及一些miRNA对精子生成的调节作用, 旨在为睾丸miRNA的进一步研究提供参考, 为利用miRNA调控和促进种公畜精液品质提供研究思路。     

microRNAs与心血管疾病

microRNAs(miRNAs)是一类长21~25 nt的非编码内源性蛋白质的RNAs,它们在转录后水平调控基因的表达,包括细胞增殖、分化和凋亡等一系列生理进程,影响生物体的生长发育,并与多种疾病相关。随着研究人员对microRNAs参与疾病的发病机制的研究,可能为人类某些疾病的治疗开辟一条新的途径。该文总结miRNAs在调控心血管疾病发生作用方面的研究成果,并对miRNA与心肌肥厚、心肌纤维化、心肌梗死、高血压、心率失常等的关系进行综述和展望。     

microRNAs与血管系统发生及疾病的研究进展

microRNAs(miRNAs)是新近发现的一类长约19-25个核苷酸的内源性微小RNA,通过与靶mRNA的5'或3'的非编码区互补结合而使靶mRNA翻译抑制或降解,在细胞增殖、分化和凋亡,胰岛素分泌,脂肪代谢及肿瘤的发生发展等多种生物学过程中起重要作用.血管是一个复杂的封闭循环性系统,其发育和疾病的发生受到多基因的调控和多因素的影响.近期的研究表明,miRNAs与血管系统的发育及其疾病的发生具有密切的关系.     

MiRNA在特发性肺纤维化中的作用

近年来研究发现微RNA（microRNA,miRNA）与机体人部分生理、病理过程均有密切关系,如：组织的发育和分化、组织再生、病毒防御以及细胞增殖与凋亡等。miRNA在特发性肺纤维化（IPF）中的作用也日渐为研究者所重视,在IPF中有些miRNA上调（如miR-155、miR-21）,有些下调（如let-7、miR-29、miR-200）。这一发现为寻找IPF治疗方法提供了一个新的突破口。本文对近年来miRNA在IPF中作用的研究进展进行了综述,并对miRNA-21、let-7d、miRNA-155、miRNA-29以及miRNA-200在肺纤维化中的作用分别进行了阐述,为研究miRNA征IPF中的作用及机制提供一定参考。     

MicroRNAs在动物皮肤和毛发发育中的调控作用

MicroRNAs(miRNAs)是近年来发现的一类由19～25个核苷酸组成的非编码单链小RNA分子,它们通过与靶基因mRNA的3′非编码区相互配对结合,在转录后水平负调控靶基因的表达.miRNA参与了包括细胞增殖、分化和凋亡及免疫系统应答在内的一系列发育调控和生物学过程.最近几年研究发现,miRNA在多种哺乳动物皮肤中均表达,并参与了哺乳动物皮肤及毛发发育的调控过程.本文综述了近几年来miRNA在各种动物皮肤及毛发发育中的表达谱以及miRNA在皮肤形态发生中的重要作用.     

MicroRNAs in skeletal and cardiac muscle development

MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs, which are approximately 22 nucleotides in length. miRNAs negatively regulate gene expression by translational repression and target mRNA degradation. It has become clear that miRNAs are involved in many biological processes, including development, differentiation, proliferation, and apoptosis. Interestingly, many miRNAs are expressed in a tissue-specific manner and several miRNAs are specifically expressed in cardiac and skeletal muscles. In this review, we focus on those miRNAs that have been shown to be involved in muscle development. Compelling evidences have demonstrated that muscle miRNAs play an important role in the regulation of muscle proliferation and differentiation processes. However, it appears that miRNAs are not essential for early myogenesis and muscle specification. Importantly, dysregulation of miRNAs has been linked to muscle-related diseases, such as cardiac hypertrophy. A mutation resulting in a gain-of-function miRNA target site in the myostatin gene leads to down regulation of the targeted protein in Texel sheep. miRNAs therefore are a new class of regulators of muscle biology and they might become novel therapeutic targets in muscle-related human diseases.     

Cardinal roles of miRNA in cardiac development and disease

MicroRNAs (miRNAs) are small noncoding RNAs that are emerging as pivotal modulators in virtually all aspects of cardiac biology, from cardiac development to cardiomyocyte survival and hypertrophy. The miRNA profiling, following gain- and loss-of-function studies using in vitro and in vivo models, has identified wide-ranging functions for miRNAs in the heart, providing new perspectives on their contributions to cardiac pathogenesis, and revealing potential therapeutic targets and diagnostic biomarkers. This review summarizes current progress in regulation of miRNAs in heart development and disease.     

miRNAs got rhythm

Despite significant advances in treatments, cardiovascular disease (CVD) remains the leading cause of human morbidity and mortality in developed countries. The development of novel and efficient treatment strategies requires an understanding of the basic molecular mechanisms underlying cardiac function. MicroRNAs (miRNAs) are a family of small nonprotein-coding RNAs that have emerged as important regulators in cardiac and vascular developmental and pathological processes, including cardiac arrhythmia, fibrosis, hypertrophy and ischemia, heart failure and vascular atherosclerosis. The miRNA acts as an adaptor for the miRNA-induced silencing complex (miRISC) to specifically recognize and regulate particular mRNAs. Mature miRNAs recognize their target mRNAs by base-pairing interactions between nucleotides 2 and 8 of the miRNA (the seed region) and complementary nucleotides in the 3'-untranslated region (3'-UTR) of mRNAs and miRISCs subsequently inhibit gene expression by targeting mRNAs for translational repression or cleavage. In this review we summarize the basic mechanisms of action of miRNAs as they are related to cardiac arrhythmia and address the potential for miRNAs to be therapeutically manipulated in the treatment of arrhythmias.     

MicroRNA-processing enzyme Dicer is required in epicardium for coronary vasculature development

The epicardium is a sheet of epithelial cells covering the heart during early cardiac development. In recent years, the epicardium has been identified as an important contributor to cardiovascular development, and epicardium-derived cells have the potential to differentiate into multiple cardiac cell lineages. Some epicardium-derived cells that undergo epithelial-to-mesenchymal transition and delaminate from the surface of the developing heart subsequently invade the myocardium and differentiate into vascular smooth muscle of the developing coronary vasculature. MicroRNAs (miRNAs) have been implicated broadly in tissue patterning and development, including in the heart, but a role in epicardium is unknown. To examine the role of miRNAs during epicardial development, we conditionally deleted the miRNA-processing enzyme Dicer in the proepicardium using Gata5-Cre mice. Epicardial Dicer mutant mice are born in expected Mendelian ratios but die immediately after birth with profound cardiac defects, including impaired coronary vessel development. We found that loss of Dicer leads to impaired epicardial epithelial-to-mesenchymal transition and a reduction in epicardial cell proliferation and differentiation into coronary smooth muscle cells. These results demonstrate a critical role for Dicer, and by implication miRNAs, in murine epicardial development.     

MicroRNAs and cardiovascular diseases

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have gained status as important regulators of gene expression. Recent studies have demonstrated that miRNAs are aberrantly expressed in the cardiovascular system under some pathological conditions. Gain- and loss-of-function studies using in vitro and in vivo models have revealed distinct roles for specific miRNAs in cardiovascular development and physiological function. The implications of miRNAs in cardiovascular disease have recently been recognized, representing the most rapidly evolving research field. In the present minireview, the current relevant findings on the role of miRNAs in cardiac diseases are updated and the target genes of these miRNAs are summarized.