MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease

Abstract

MicroRNAs play central roles in cardiovascular disease, and their therapeutic manipulation raises exciting opportunities as well as challenges in the path toward clinical development.

Fig. 1. miRNA regulation and processing

miRNAs associate with the AGO protein in the RISC complex and bind to the 3′UTRs of target mRNAs to block protein expression. Stress signals such as ischemia and cytokine signaling regulate miRNA expression and their repressive activity. miRNAs are packaged into microvesicles and exosomes and may be secreted into the bloodstream, where they are transported to adjacent cells or distal tissues. miRNAs are also found in apoptotic bodies and lipoproteins. AntimiRs targeted against miRNAs are taken up by cells and sequestered in intracellular vesicles from which they are gradually released, enabling them to associate with their miRNA targets.

Fig. 2. miRNAs in cardiovascular disease

Shown are pathological processes in the cardiovascular system and the miRNAs that control these processes. miRNAs regulate cardiomyocyte proliferation, hypertrophy, and apoptosis. Other miRNAs act on fibroblasts and inflammatory cells to control fibrosis and inflammation, respectively. Blood vessel growth and stability, and angiogenesis and smooth-muscle cell proliferation, are also regulated by miRNAs acting on endothelial cells and smooth-muscle cells, respectively.