The Greatly Under-Represented Role of Smooth Muscle Cells in Atherosclerosis

This article summarizes previous and recent research on the fundamental role of arterial smooth muscle cells (SMCs) as drivers of initial and, along with macrophages, later stages of human atherosclerosis.

Studies using human tissues and SMC lineage-tracing mice have reinforced earlier observations that SMCs drive initial atherogenesis in humans and contribute a multitude of phenotypes including foam cell formation hitherto attributed primarily to macrophages in atherosclerosis. Arterial smooth muscle cells (SMCs) are the primary cell type in human pre-atherosclerotic intima and are responsible for the retention of lipoproteins that drive the development of atherosclerosis. Despite this, images of atherogenesis still depict the process as initially devoid of SMCs, primarily macrophage driven, and indicate only relatively minor roles such as fibrous cap formation to intimal SMCs. This review summarizes historical and recent observations regarding the importance of SMCs in the formation of a pre-atherosclerotic intima, initial and later foam cell formation, and the phenotypic changes that give rise to multiple different roles for SMCs in human and mouse lesions. Potential SMC-specific therapies in atherosclerosis are presented.