MicroRNAs as a therapeutic target for cardiovascular diseases

Introduction Biogenesis of miRNAs and their regulatory mechanisms MiRNAs in cardiovascular diseases MiRNAs in hypertrophy MiRNAs in cardiac fibrosis MiRNAs in arrhythmia MiRNAs in myocardial infarction MiRNAs in heart failure MiRNAs in angiogenesis MiRNAs in cardiomyopathy MiRNAs in antherogenesis Role of Dicer in cardiomyopathy MiRNAs - a new strategy for treatment of cardiovascular diseases MiRNA - an innovative therapeutic approach MiRNAs in stem cell therapy A new candidate in microRNomics Therapeutic challenges and their remedies Mode of delivery of miRNAs Role of microevironment Approaches of miRNAs in cardiovascular therapy MicroRNAs (miRNAs) are tiny, endogenous, conserved, non-coding RNAs that negatively modulate gene expression by either promoting the degradation of mRNA or down-regulating the protein production by translational repression. They maintain optimal dose of cellular proteins and thus play a crucial role in the regulation of biological functions. Recent discovery of miRNAs in the heart and their differential expressions in pathological conditions provide glimpses of undiscovered regulatory mechanisms underlying cardiovascular diseases. Nearly 50 miRNAs are overexpressed in mouse heart. The implication of several miRNAs in cardiovascular diseases has been well documented such as miRNA-1 in arrhythmia, miRNA-29 in cardiac fibrosis, miRNA-126 in angiogenesis and miRNA-133 in cardiac hypertrophy. Aberrant expression of Dicer (an enzyme required for maturation of all miRNAs) during heart failure indicates its direct involvement in the regulation of cardiac diseases. MiRNAs and Dicer provide a particular layer of network of precise gene regulation in heart and vascular tissues in a spatiotemporal manner suggesting their implications as a powerful intervention tool for therapy. The combined strategy of manipulating miRNAs in stem cells for their target directed differentiation and optimizing the mode of delivery of miRNAs to the desired cells would determine the future potential of miRNAs to treat a disease. This review embodies the recent progress made in microRNomics of cardiovascular diseases and the future of miRNAs as a potential therapeutic target - the putative challenges and the approaches to deal with it.