Scalbert Elizabeth, Bril Antoine
Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
Curr Opin Pharmacol. 2008 Apr;8(2):181-8. doi: 10.1016/j.coph.2007.12.013. Epub 2008 Feb 19.
MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that regulate about 30% of protein-coding genes of the human genome. Thus far, more than 400 miRNAs have been cloned and sequenced in humans. Their biological importance, initially demonstrated in cancer, viral diseases and developmental processes, was more recently investigated in cardiovascular physiology and pathology. MiRNAs expression is tightly controlled in a tissue-specific and developmental stage-specific manner and some of them are highly and specifically expressed in cardiovascular tissues. Through the regulation of the expression of genes involved in cell growth, contractility and electrical conductance, cardiac miRNAs may play a major role in heart development and function. In vascular cells, miRNAs have been linked to vasculoproliferative conditions such as angiogenesis and neointimal lesion formation. Diagnostic use and therapeutic modulation of individual miRNAs or miRNA clusters in cardiovascular diseases will have to be further explored in the future. Molecules specifically regulating cardiovascular miRNAs, either mimicking or antagonizing miRNAs actions, will hopefully normalize dysfunctional gene networks and constitute a new therapy paradigm of cardiovascular diseases.
微小RNA(miRNA)是内源性的小非编码RNA,可调控人类基因组中约30%的蛋白质编码基因。迄今为止,人类已克隆并测序了400多种miRNA。其生物学重要性最初在癌症、病毒疾病和发育过程中得到证实,最近在心血管生理学和病理学中也有研究。miRNA的表达以组织特异性和发育阶段特异性的方式受到严格控制,其中一些在心血管组织中高度特异性表达。通过调节参与细胞生长、收缩性和电传导的基因表达,心脏miRNA可能在心脏发育和功能中发挥重要作用。在血管细胞中,miRNA与血管增殖性疾病如血管生成和新生内膜病变形成有关。未来还需进一步探索心血管疾病中单个miRNA或miRNA簇的诊断用途和治疗调节。特异性调节心血管miRNA的分子,无论是模拟还是拮抗miRNA的作用,有望使功能失调的基因网络正常化,并构成心血管疾病的新治疗模式。