MicroRNAs as a therapeutic target for cardiovascular diseases

Abstract

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.

Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development

“…Unlike most traditional therapeutic approaches in which drugs have specific cellular targets, the key component of miR modulation lies in regulation of entire functional gene networks (25). However, this is also a potential weakness of the approach, as unintended off-target effects may occur.…”

Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

“…MicroRNAs are small (ϳ22 nt), noncoding RNAs that regulate mRNA and protein expression through mRNA degradation or translational inhibition (10). MiRNAs are rapidly emerging as therapeutic targets for CVD (22,103,108,122,126). H 2 S regulates miRNA expression (70,73,93); however, the interaction between H 2 S and miRNAs in CVD is poorly understood.…”

Novel modulators of senescence, aging, and longevity: Small non-coding RNAs enter the stage

“…Finally, small non-coding RNAs and RNAi have already been introduced as promising novel drugs in preclinical and clinical trials against various diseases (Blenkiron and Miska, 2007;Lopez-Fraga et al, 2009;Mishra et al, 2009b;Nakasa et al, 2009;Takeshita et al, 2009;Zhang, 2009). The power of small ncRNAs and their derivatives as putative therapeutic molecules together with the still scarce functional knowledge about non-coding RNAs in regard to aging gives all reason to expect many surprises for basic and biomedical aging research in regard to nonconding RNAs.…”