Roles of Vascular Smooth Muscle Cells in Atherosclerotic Calcification

The accumulation of calcium in atherosclerotic plaques is a prominent feature of advanced atherosclerosis, and it has a strong positive correlation with the total burden of atherosclerosis. Atherosclerotic calcification usually appears first at the necrotic core, indicating that cell death and inflammatory processes are involved in calcification. During atherosclerotic inflammation, various cell types, such as vascular smooth muscle cells, nascent resident pericytes, circulating stem cells, or adventitial cells, have been assumed to differentiate into osteoblastic cells, which lead to vascular calcification. Among these cell types, vascular smooth muscle cells are considered a major contributor to osteochondrogenic cells in the atherosclerotic milieu. In this review, we summarize the molecular mechanisms underlying the osteochondrogenic switch of vascular smooth muscle cells in atherosclerotic plaques.