Dhore C R, Cleutjens J P, Lutgens E, Cleutjens K B, Geusens P P, Kitslaar P J, Tordoir J H, Spronk H M, Vermeer C, Daemen M J
Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Netherlands.
Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1998-2003. doi: 10.1161/hq1201.100229.
In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification.
在本研究中，我们检测了人类动脉粥样硬化中骨形成和破骨细胞生成调节因子的表达情况，因为越来越多的证据表明动脉粥样硬化钙化与骨钙化具有共同特征。本研究最显著的发现是，在未患病的主动脉中，基质Gla蛋白、骨钙素和骨唾液蛋白呈组成性免疫反应性，而在未患病的主动脉和早期动脉粥样硬化病变中，骨形态发生蛋白（BMP）-2、BMP-4、骨桥蛋白和骨连接蛋白缺失。当动脉粥样硬化斑块出现钙化或骨形成时，BMP-2、BMP-4、骨桥蛋白和骨连接蛋白上调。有趣的是，这种上调与基质Gla蛋白、骨钙素和骨唾液蛋白的持续免疫反应性相关。破骨细胞生成的两种调节因子（骨保护素[OPG]及其配体OPGL）存在于未患病的血管壁和早期动脉粥样硬化病变中。在晚期钙化病变中，OPG存在于骨结构中，而OPGL仅存在于钙沉积物周围的细胞外基质中。观察到的表达模式表明，在人类动脉粥样硬化发生过程中，骨基质调节蛋白的表达受到严格调控。动脉粥样硬化发生过程中OPG和OPGL的表达模式可能表明这些蛋白不仅在破骨细胞生成中起调节作用，而且在动脉粥样硬化钙化中也起调节作用。
