MECHANISM OF CALCIFICATION IN ATHEROSCLEROSIS

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, hydroxyapa tite, and several features of its development suggest a mechanism simi lar to osteogenesis and not merely passive precipitation. The artery w ad has been shown to contain several bone-related proteins, including those for osteopontin, osteonectin, and osteocalcin, as well as proteo glycan cove proteins homologous with bone biglycan. Our laboratory rec ently demonstrated that a potent osteogenic differentiation factor, bo ne morphogenetic protein 2a, is expressed in calcified human atheroscl erotic lesions, suggesting that arterial calcification may be initiate d by an osteogenic differentiation. In addition, a cell capable of cal cium mineral formation in vitro has been isolated from bovine and huma n aorta and identified by immunostaining as having a surface marker ch aracteristic of microvascular pericytes. These findings suggest the po ssibility that plaque calcification develops when ;a signal from ather osclerotic plaque or a factor associated with atherosclerosis induces expression of bone morphogenetic protein, leading to osteogenic differ entiation of pluripotential, pericytelike cells located in the arteria l intima, which then produce bonelike matrix and hydroxyapatite minera l. These findings also raise questions as to whether osteogenic-promot ing factors used to prevent osteoporosis may also increase risk of art erial calcification.