Association of osteopontin with calcification in human mitral valves

Little is known about the long-standing inflammation leading to calcification within heart valves. Osteopontin, a phosphorylated glycoprotein, is present within atheromatous calcific plagues in response to vascular endothelial injury. The purpose of the study was to investigate whether osteopontin exists in calcific mitral valve leaflets in human beings, and to determine a link between chronic inflammation leading to mitral stenosis and the osteopontin status of mitral valvular tissue.

We reviewed the case histories of 17 patients who underwent mitral valve replacement therapy for mitral stenosis between 1995 and 1997 (8 men and 9 women, mean age 61 years). Hybrid mouse monoclonal immunoglobulin G1 antibodies were used for immunohistochemical detection of osteopontin in the acetone-fixed specimen. The control group consisted of normal mitral valve tissue from cardiomyopathy patients who underwent cardiac transplantation.

A weak osteopontin immunoreactivity was present in apparently normal mitral valve tissue obtained from cardiomyopathy patients. All mitral stenosis patients had immunoreactivity (17/17) for osteopontin within calcific deposits of mitral valve tissue. The intensity of osteopontin activity had a strong association with increasing macrophage and calcium aggregations in the mitral valvular tissue. We found no correlation between osteopontin status and clinical features on the prognosis of calcific mitral stenosis.

We conclude that osteopontin coexists with intimal macrophages in calcific human mitral valve tissue. Demonstration of such association between the presence of osteopontin and calcification in human mitral valves is consistent with the hypothesis that calcification in this tissue is, at least in part, an actively mediated phenomenon.