Wang Zhiguo, Luo Xioabin, Lu Yanjie, Yang Baofeng
Research Center, Montreal Heart Institute, Montreal, PQ H1T 1C8, Canada.
J Mol Med (Berl). 2008 Jul;86(7):771-83. doi: 10.1007/s00109-008-0341-3. Epub 2008 Apr 16.
Cardiovascular disease is among the main causes of morbidity and mortality in developed countries. The pathological process of the heart is associated with altered expression profile of genes that are important for cardiac function. MicroRNAs (miRNAs) have emerged as one of the central players of gene expression regulation. The implications of miRNAs in the pathological process of cardiovascular system have recently been recognized, representing the most rapidly evolving research field. Here, we summarize and analyze the currently available data from our own laboratory and other groups, providing a comprehensive overview of miRNA function in the heart, including a brief introduction of miRNA biology, expression profile of miRNAs in cardiac tissue, role of miRNAs in cardiac hypertrophy and heart failure, the arrhythmogenic potential of miRNAs, the involvement of miRNAs in vascular angiogenesis, and regulation of cardiomyocyte apoptosis by miRNAs. The target genes and signaling pathways linking the miRNAs to cardiovascular disease are highlighted. The applications of miRNA interference technologies for manipulating miRNA expression, stability, and function as new strategies for molecular therapy of human disease are evaluated. Finally, some specific issues related to future directions of the research on miRNAs relevant to cardiovascular disease are pinpointed and speculated.
心血管疾病是发达国家发病和死亡的主要原因之一。心脏的病理过程与对心脏功能至关重要的基因表达谱改变有关。微小RNA(miRNA)已成为基因表达调控的核心参与者之一。最近,人们已经认识到miRNA在心血管系统病理过程中的作用,这代表了发展最迅速的研究领域。在这里,我们总结并分析了来自我们自己实验室和其他研究小组的现有数据,全面概述了miRNA在心脏中的功能,包括miRNA生物学的简要介绍、miRNA在心脏组织中的表达谱、miRNA在心肌肥大和心力衰竭中的作用、miRNA的致心律失常潜力、miRNA参与血管生成以及miRNA对心肌细胞凋亡的调节。重点介绍了将miRNA与心血管疾病联系起来的靶基因和信号通路。评估了miRNA干扰技术在操纵miRNA表达、稳定性和功能方面作为人类疾病分子治疗新策略的应用。最后,指出并推测了与心血管疾病相关miRNA研究未来方向的一些具体问题。