New therapeutic potential of microRNA treatment to target vulnerable atherosclerotic lesions and plaque rupture

Abstract

Purpose of review: Atherosclerotic lesion vulnerability leading to plaque rupture is a major cause of morbidity in western society. Although several recent major trials have identified statins and angiotensin-converting enzyme inhibitors as having a pleiotropic benefit, no current therapeutic regime directly targets atherosclerosis. The emerging functions of microRNAs (miRs) in regulating gene expression have opened diverse possibilities in understanding plaque biology and in offering new therapeutic strategies. In this review, we consider vascular endothelial cells, smooth muscle cells and monocytes as the main cellular participants in vessel homeostasis during atherosclerosis evolution and discuss how they are functionally modified by miRs and how these modifications may allow therapeutic targeting. Recent findings: Emerging roles for miRs in the pro-inflammatory functions of monocytes and macrophages, and proangiogenic functions of endothelial cells, suggest that miRs regulating these processes are potential targets. Conversely, the contribution of smooth muscle cells to plaque integrity may be augmented by miR-based agents. Recent investigations have uncovered key roles for miRs in each of these areas, which may be targeted through either silencing of proatherogenic or augmentation of antiatherogenic pathways. Summary: With emerging miR-based therapeutics, a new paradigm for therapeutic intervention with the ultimate goal of plaque stabilization may exist. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.