Abstract:
Alterations in the vascular smooth muscle cells (VSMC) phenotype play a critical role in the pathogenesis of several cardiovascular diseases, including hypertension, atherosclerosis, and restenosis after angioplasty. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (approximately 19-25 nucleotides in length) that function as regulators in various physiological and pathophysiological events. Recent studies have suggested that aberrant miRNAs\' expression might underlie VSMC phenotypic transformation, appearing to regulate the phenotypic transformations of VSMCs by targeting specific genes that either participate in the maintenance of the contractile phenotype or contribute to the transformation to alternate phenotypes, and affecting atherosclerosis, hypertension, and coronary artery disease by altering VSMC proliferation, migration, differentiation, inflammation, calcification, oxidative stress, and apoptosis, suggesting an important regulatory role in vascular remodeling for maintaining vascular homeostasis. This review outlines recent progress in the discovery of miRNAs and elucidation of their mechanisms of action and functions in VSMC phenotypic regulation. Importantly, as the literature supports roles for miRNAs in modulating vascular remodeling and for maintaining vascular homeostasis, this area of research will likely provide new insights into clinical diagnosis and prognosis and ultimately facilitate the identification of novel therapeutic targets.
摘要:
血管平滑肌细胞(VSMC)表型的改变在几种心血管疾病的发病机制中起着至关重要的作用。包括高血压,动脉粥样硬化,血管成形术后再狭窄.MicroRNAs(miRNA)是一类内源性非编码RNA(长度约19-25个核苷酸),在各种生理和病理生理事件中充当调节剂。最近的研究表明,异常的miRNA表达可能是VSMC表型转化的基础,似乎通过靶向参与维持收缩表型或有助于转化为替代表型的特定基因来调节VSMC的表型转化,影响动脉粥样硬化,高血压,和冠状动脉疾病通过改变VSMC增殖,迁移,分化,炎症,钙化,氧化应激,和细胞凋亡,提示在维持血管稳态的血管重塑中的重要调节作用。本文综述了miRNA的发现及其在VSMC表型调控中的作用机制和功能的研究进展。重要的是,由于文献支持miRNA在调节血管重塑和维持血管稳态中的作用,这一领域的研究可能为临床诊断和预后提供新的见解,并最终促进新的治疗靶点的识别。