DIFFUSE CALCIFICATION IN HUMAN CORONARY-ARTERIES - ASSOCIATION OF OSTEOPONTIN WITH ATHEROSCLEROSIS

Coronary atherosclerosis is frequently associated with calcification o f arterial plaque. To understand the mechanisms responsible for the fo rmation of atherosclerotic calcification, we examined human coronary a rteries for the presence and extent of mineral. In sections stained sp ecifically for mineral, staining was diffuse and present in all athero sclerotic plaques. Hydroxyapatite was not detected in normal coronary artery sections. Distribution of hydroxyapatite coincided with a simil ar distribution of calcium detected by a radiodense pattern using cont act microradiography of the same sections before cytochemical staining . By energy-dispersive x-ray microanalysis, the chemical composition o f calcified sites was identical to hydroxyapatite (Ca-10[PO4](6)[OH](2 )), the major inorganic component of bone. Osteopontin is a phosphoryl ated glycoprotein with known involvement in the formation and calcific ation of bone and is regulated by local cytokines. Human coronary arte ry segments (14 normal and 34 atherosclerotic) obtained at autopsy wer e evaluated immunohistochemically using polyclonal antibodies generate d against human osteopontin. Immunohistochemistry for osteopontin indi cated intense, highly specific staining in the outer margins of all di seased segments at each calcification front; staining was evident thro ughout the entire plaque. Conversely, arterial segments free of athero ma and calcification and sections treated with nonimmune serum had no evidence of positive staining. Osteopontin, a protein involved in mine ralization is specifically associated with calcific coronary atheroma and may play an important role in the onset and progression of this di sease in human coronary arteries. The deposition of noncollagenous pro teins such as osteopontin may regulate the presence or absence of calc ification and ultimately alter vessel compliance.