O'Brien K D, Kuusisto J, Reichenbach D D, Ferguson M, Giachelli C, Alpers C E, Otto C M
Department of Medicine, University of Washington, Seattle 98195, USA.
Circulation. 1995 Oct 15;92(8):2163-8. doi: 10.1161/01.cir.92.8.2163.
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.
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.
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.
三叶主动脉瓣的非风湿性狭窄以钙化显著为特征，曾被称为“退行性”疾病，但最近有研究表明，慢性炎症是主动脉狭窄病变发展过程中的一个特征。这一观察结果提示主动脉瓣钙化可能受到主动调节。因此，本研究调查了在主动脉瓣狭窄病变中是否能检测到骨桥蛋白，该蛋白与正常钙化和营养不良性钙化的调节均有关。
对14个人类主动脉瓣进行了形态学和免疫组织化学研究，这些瓣膜代表了从正常到临床狭窄的一系列病理状态。对钙化程度、巨噬细胞积聚情况及其与骨桥蛋白表达的关系进行了分析。在主动脉狭窄早期至晚期病变中，骨桥蛋白表达程度与钙化程度和巨噬细胞积聚程度之间均存在高度显著的统计学关联。此外，原位杂交将骨桥蛋白mRNA定位到病变巨噬细胞的一个亚群。
这些结果表明，主动脉狭窄中的钙化可能并非是一个退行性且不可改变的过程，部分可能是一个受主动调节的过程，有通过调节炎症或合成如骨桥蛋白等可调节该组织钙化的蛋白质来加以控制的潜力。
