MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype

In periods of health, the vascular smooth muscle cell (VSMC) predominantly functions to regulate vascular tone and to provide structural integrity to the vascular tree. However, the VSMC is also one of the most plastic cells in the body. Under periods of stress, or in response to disease stimuli, the VSMC deviates from its physiologic state and can become hyperproliferative, migratory and/or proinflammatory. Such de-differentiation is believed to contribute to a variety of maladaptive processes with relevance to vascular disease, including de novo atherogenesis, postangioplasty neointimal hyperplasia, aneurysmal degeneration, medial calcinosis, and even foam cell formation. In an effort to modulate these conditions, scientists have sought the master regulators of VSMC physiology and plasticity, and have made progress identifying a number of transcriptional cofactors that modulate expression of the contractile apparatus and genes which are activated in the perturbed VSMC. Recent work, however, has shown that several epigenetic factors also modify VSMC behavior and could similarly serve as translational targets or biomarkers of disease. In the review provided below, we will focus on the role of microRNAs as the best studied of these factors, and provide an overview of their important role in VSMC homeostasis and pathophysiology.In the nondiseased artery, the tunica media is comprised almost exclusively of VSMCs and the connective tissues secreted by these cells. The VSMC serves to modulate vascular tone, and therefore, end-organ perfusion, by contracting and relaxing in response to sympathetic innervation and diffusible factors, such as nitric oxide released from the overlying endothelial cells of the tunica intima.1–3 Their related extracellular matrix proteins comprise the scaffolding, which provide the structural support necessary to withstand the radial force applied to the vessel during the cardiac cycle. At the molecular level, the VSMC is dominated …