Role of Diverse Smooth Muscle Cell Phenotypic Transitions in Atherosclerosis Development and Late-Stage Pathogenesis

Major adverse cardiovascular events resulting from atherosclerotic plaque instability account for a plurality of deaths worldwide despite the use of highly effective lipid-lowering therapies. Over the last three decades, the role of inflammation in atherogenesis has been tested extensively. Although preclinical studies demonstrate a clear role for inflammation in atherogenesis, clinical studies using global anti-inflammatory therapies have not been as successful as hoped, encouraging the search for new therapeutic strategies. Thanks to the advent of cell-specific lineage tracing, we have begun to appreciate the multifaceted role of smooth muscle cell phenotypic switching in modulating plaque stability. Here, we review the mechanisms controlling smooth muscle cell phenotypic switching during early and late-stage pathogenesis, which may inspire future therapies to stabilize plaques.