(Circulation. 1995;92:2163-2168.)
© 1995 American Heart Association, Inc.
Articles |
Osteopontin Is Expressed in Human Aortic Valvular Lesions
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.
From the Division of Cardiology, Department of Medicine (K.D.O., J.K., C.M.O.), and Department of Pathology (D.D.R., M.F., C.G., C.E.A.), University of Washington, Seattle.
Background Nonrheumatic stenosis of trileaflet aortic valves, in which calcification is a prominent feature, has been termed a "degenerative" condition, but it has been demonstrated recently that chronic inflammation is a characteristic feature of the developing lesion of aortic stenosis. This observation raised the possibility that calcification in the aortic valve might be actively regulated. Thus, the present study investigated whether osteopontin, a protein implicated in the regulation of both normal and dystrophic calcification, could be detected in lesions of valvular aortic stenosis.
Methods and Results Morphological and immunohistochemical studies were performed on 14 human aortic valves, representing a range of pathology from normal to clinically stenotic. The extent of calcification and macrophage accumulation and their relation to the presence of osteopontin protein were characterized. Highly statistically significant associations were found between the degree of osteopontin expression and the degrees of both calcification and macrophage accumulation in early through late lesions of aortic stenosis. Further, in situ hybridization localized osteopontin mRNA to a subset of lesion macrophages.
Conclusions These results suggest that, rather than representing a degenerative and unmodifiable process, calcification in aortic stenosis may be, in part, an actively regulated process with the potential for control either through modification of inflammation or synthesis of proteins such as osteopontin, which may modulate calcification in this tissue.
Key Words: osteopontin • aorta • valves • stenosis • calcium
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