OSTEOPONTIN IS EXPRESSED IN HUMAN AORTIC VALVULAR LESIONS
OSTEOPONTIN IS EXPRESSED IN HUMAN AORTIC VALVULAR LESIONS
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DOI：
10.1161/01.cir.92.8.2163
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发表时间：
1995-10-15
期刊：
影响因子：
37.8
通讯作者：
OTTO, CM
中科院分区：
文献类型：
--
作者：
OBRIEN, KD;KUUSISTO, J;OTTO, CM
背景：以钙化为主要特征的三叶主动脉瓣非风湿性狭窄被称为“退行性”疾病，但最近研究表明慢性炎症是主动脉瓣狭窄病变的特征性表现。这一观察结果提出了主动调节主动脉瓣钙化的可能性。因此，本研究调查是否骨桥蛋白，一种蛋白质参与正常和营养不良性钙化的调节，可以检测到病变的主动脉瓣stenosis.Methods和Results形态学和免疫组化研究进行了14人主动脉瓣，代表一系列的病理从正常到临床狭窄。表征了钙化和巨噬细胞积聚的程度及其与骨桥蛋白存在的关系。在主动脉瓣狭窄的早期至晚期病变中，骨桥蛋白表达程度与钙化和巨噬细胞积聚程度之间存在高度统计学显著相关性。此外，原位杂交定位骨桥蛋白mRNA的一个子集的病变macrophages.Conclusions这些结果表明，而不是代表一个退行性和不可改变的过程，钙化在主动脉瓣狭窄可能是，在一定程度上，一个积极调节的过程，通过修改炎症或蛋白质的合成，如骨桥蛋白，这可能会调节钙化在这个组织的控制潜力。
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.