Smooth muscle cells in atherosclerosis: essential but overlooked translational perspectives

Abstract Smooth muscle cells have been identified as the most abundant cell type present in the atherosclerotic plaque, the culprit underlying most cardiovascular diseases and their fatal outcomes. Despite their crucial role in plaque formation and progression, smooth muscle cells do not receive as much attention as inflammatory or endothelial cells. The purpose of this review is to examine the roles of smooth muscle cells in the pathogenesis of atherosclerosis and their potential as therapeutic targets. A comprehensive overview of current insights into smooth muscle cell phenotypic diversity, function, and spatial localization within stable and unstable plaques, focusing on their relevance to human pathology is discussed. The review also addresses the contribution of clonal expansion of smooth muscle cells in plaque progression, evaluates emerging diagnostic tools which may reflect smooth muscle cell physiology, and highlights strategies to modulate smooth muscle cell behaviour for improved cardiovascular outcomes. Special attention is given to the clinical translation of these therapies, considering the challenges and opportunities in leveraging smooth muscle cells as therapeutic targets.