Mechanism of calcification in atherosclerosis

Abstract

Calcification is commonly associated with atherosclerosis, and it has important clinical implications, especially in coronary arteries. The mineral has been identified as the same mineral as in bone, hydroxyapatite, and several features of its development suggest a mechanism similar to osteogenesis and not merely passive precipitation. The artery wall has been shown to contain several bone-related proteins, including those for osteopontin, osteonectin, and osteocalcin, as well as proteoglycan core proteins homologous with bone biglycan. Our laboratory recently demonstrated that a potent osteogenic differentiation factor, bone morphogenetic protein 2a, is expressed in calcified human atherosclerotic lesions, suggesting that arterial calcification may be initiated by an osteogenic differentiation. In addition, a cell capable of calcium mineral formation in vitro has been isolated from bovine and human aorta and identified by immunostaining as having a surface marker characteristic of microvascular pericytes. These findings suggest the possibility that plaque calcification develops when a signal from atherosclerotic plaque or a factor associated with atherosclerosis induces expression of bone morphogenetic protein, leading to osteogenic differentiation of pluripotential, pericytelike cells located in the arterial intima, which then produce bonelike matrix and hydroxyapatite mineral. These findings also raise questions as to whether osteogenic-promoting factors used to prevent osteoporosis may also increase risk of arterial calcification.