Targeting vascular smooth muscle cells with natural compounds to combat atherosclerosis

Cardiovascular disease (CVD) is a leading cause of global morbidity and mortality, with atherosclerosis (AS) recognized as the primary underlying pathology of chronic cardiovascular disorders. AS is a progressive and sustained inflammatory condition characterized by excessive lipid accumulation, oxidative stress, inflammatory responses, plaque formation and rupture, thrombus development, and vascular calcification (VC). Vascular smooth muscle cells (VSMCs) are essential components of the vascular wall, and their proliferation, migration, phenotypic modulation, senescence, and death significantly influence AS progression. The precise mechanisms by which VSMCs contribute to AS pathogenesis have become a major focus of research. In recent years, numerous natural compounds have attracted increasing attention in AS research due to their multi-targeted effects and low toxicity profiles. However, a comprehensive review specifically addressing natural compounds that ameliorate AS via modulation of VSMCs remains lacking. This article critically examines the pivotal roles of VSMCs in AS pathophysiology and the regulatory effects of natural compounds on VSMC metabolism. A summary of pharmacological actions and potential molecular targets is provided to clarify the diverse functional roles of VSMCs, offering valuable insights for the development of novel and effective anti-atherosclerotic therapies.