Vascular Smooth Muscle Cells in the Pathogenesis of Vascular Calcification

Abstract

See related article, pages 733–741 Vascular calcification is a major risk factor for cardiovascular morbidity and mortality. In atherosclerotic lesions, calcification is mainly found in the neointima of atheromatous plaques and has been shown to positively correlate with the plaque burden and the risk of myocardial infarction. Calcification of atherosclerotic plaques has been clearly shown to result from osteoblastic differentiation of cells in the neointima forming a mineralized matrix-containing type I collagen similar to bone formation.1–3 The origin of the neointimal osteoblastic cells remains controversial, but evidence that they derive from migratory smooth muscle cells is growing. Atherosclerotic calcification is increased by chronic kidney disease, type 2 diabetes mellitus, and aging. However, another form of vascular calcification, that of the vascular media, known as Monckeberg’s medial calcific sclerosis, is also prevalent in patients with chronic kidney disease, in type 2 diabetes mellitus, and in aging patients, especially those with osteoporosis. Medial calcification in these patients can occur independently of intimal atherosclerotic lesions and features linear calcium phosphate deposits along the elastic lamellae, which may form circumferential mineral deposits throughout the media. Medial calcification causes vascular stiffness and increased pulse wave velocity that causes cardiac dysfunction/ischemia. Mineralization of elastin is clearly different from osteoblastic bone formation, and the pathogenesis of medial calcification is less clear than that of atherosclerosis. Osteochondroblastic differentiation has been detected in cells adjacent to medial calcific deposits …