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microRNAs (miRs) are short, approximately 22-nucleotide-long non-coding RNAs involved in the control of gene expression. They guide ribonucleoprotein complexes that effect translational repression or messenger RNA degradation to targeted messenger RNAs. miRs were initially thought to be peculiar to the developmental regulation of the nematode worm, in which they were first described in 1993. Since then, hundreds of different miRs have been reported in diverse organisms, and many have been implicated in the regulation of physiological processes of adult animals. Of importance, misexpression of miRs has been uncovered as a pathogenic mechanism in several diseases. Here, we first outline the biogenesis and mechanism of action of miRs, and then discuss their relevance to heart biology, pathology, and medicine.

MicroRNA (miRNA) is the term used to describe endogenous, short (19-25 nucleotide long) regulatory RNA molecules that govern gene expression at the post-transcriptional level. They were initially thought of as a curiosity limited to the developmental timing of roundworms when the founding members were discovered in the early 1990s. They are now acknowledged as a fundamental regulator of gene expression for the development of many organisms. The importance of miRNA in biological processes of mammals other than development has recently surfaced, and the first report on the role of miRNAs in the heart was published in 2005. intense studies are being conducted to elucidate the physiologic pathways regulated by miRNAs in this organ and how miRNAs are involved in cardiovascular pathology. Here, we comprehensively review what has been published on mirNA and heart disease to date.

MicroRNA has been shown to be essential for correct cardiovascular development and physiology in a number of recent reports. Studies have also started to characterize the link between specific microRNAs and aspects of pathogenesis--such as chamber morphogenesis, conduction, and contraction--and between microRNA expression signatures and pathological cardiac phenotypes--such as hypertrophy, ischemic cardiomyopathy, dilated cardiomyopathy, and aortic stenosis. Congenital anomalies of the heart may also be associated with the dysregulation of specific microRNAs. Here we report on the latest findings.

Growing evidence indicates that microRNAs (miRNAs) are involved in a variety of basic biological processes, including cell proliferation, apoptosis, stress response, hematopoesis, and oncogenesis. In fact, bioinformatic analysis predicts that each miRNA may regulate hundreds of targets, suggesting that miRNAs may play roles in almost every biological pathway. Information from recent studies indicate that miRNAs are involved in the regulation of cardiac development and pathophysiology. Notably, knockout of miRNA-1 was associated with cardiac defects, including regulation of cardiac morphogenesis, electrical conduction, and cell cycle control. Our group has identified a critical role of miRNA-1 and miRNA-133 in determining cardiac hypertrophy and has shown an inverse correlation of expression with cardiac hypertrophy, in vitro, in murine models and in human disease states associated with cardiac hypertrophy. Remarkably, in vivo experiments with a single infusion of antagomir-133 oligonucleotide, a small cholesterol-conjugated RNA sequence suppressing endogenous miRNA, induced marked and sustained cardiac hypertrophy. Shedding light on the role of this new class of RNA molecules in heart physiology and pathology may reveal possible future therapeutic applications for the treatment of heart diseases. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that microRNAs (miRNAs or miRs) are involved in basic cell functions and oncogenesis. Here we report that miR-133 has a critical role in determining cardiomyocyte hypertrophy. We observed decreased expression of both miR-133 and miR-1, which belong to the same transcriptional unit, in mouse and human models of cardiac hypertrophy. In vitro overexpression of miR-133 or miR-1 inhibited cardiac hypertrophy. In contrast, suppression of miR-133 by 'decoy' sequences induced hypertrophy, which was more pronounced than that after stimulation with conventional inducers of hypertrophy. In vivo inhibition of miR-133 by a single infusion of an antagomir caused marked and sustained cardiac hypertrophy. We identified specific targets of miR-133: RhoA, a GDP-GTP exchange protein regulating cardiac hypertrophy; Cdc42, a signal transduction kinase implicated in hypertrophy; and Nelf-A/WHSC2, a nuclear factor involved in cardiogenesis. Our data show that miR-133, and possibly miR-1, are key regulators of cardiac hypertrophy, suggesting their therapeutic application in heart disease. [ABSTRACT FROM AUTHOR]