Shanahan C M, Cary N R, Metcalfe J C, Weissberg P L
Department of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
J Clin Invest. 1994 Jun;93(6):2393-402. doi: 10.1172/JCI117246.
Calcification is common in atheromatous plaques and may contribute to plaque rupture and subsequent thrombosis. However, little is known about the mechanisms which regulate the calcification process. Using in situ hybridization and immunohistochemistry we show that two bone-associated proteins, osteopontin (OP) and matrix Gla protein (MGP), are highly expressed in human atheromatous plaques. High levels of OP mRNA and protein were found in association with necrotic lipid cores and areas of calcification. The predominant cell type in these areas was the macrophage-derived foam cell, although some smooth muscle cells could also be identified. MGP was expressed uniformly by smooth muscle cells in the normal media and at high levels in parts of the atheromatous intima. Highest levels of this matrix-associated protein were found in lipid-rich areas of the plaque. The pattern of expression of these two genes contrasted markedly with that of calponin and SM22 alpha, genes expressed predominantly by differentiated smooth muscle cells and whose expression was generally confined to the media of the vessel. The postulated function of OP and MGP as regulators of calcification in bone and the high levels and colocalization of both in atheromatous plaques suggest they have an important role in plaque pathogenesis and stability.
钙化在动脉粥样硬化斑块中很常见，可能导致斑块破裂及随后的血栓形成。然而，关于调节钙化过程的机制我们却知之甚少。通过原位杂交和免疫组织化学方法，我们发现两种与骨相关的蛋白，骨桥蛋白（OP）和基质Gla蛋白（MGP），在人类动脉粥样硬化斑块中高度表达。在坏死脂质核心及钙化区域发现高水平的OP mRNA和蛋白。这些区域的主要细胞类型是巨噬细胞衍生的泡沫细胞，不过也能识别出一些平滑肌细胞。MGP在正常中膜的平滑肌细胞中均匀表达，在动脉粥样硬化内膜的部分区域高水平表达。在斑块富含脂质的区域发现这种基质相关蛋白的水平最高。这两个基因的表达模式与钙调蛋白和SM22α明显不同，钙调蛋白和SM22α主要由分化的平滑肌细胞表达，其表达通常局限于血管中膜。OP和MGP在骨中作为钙化调节因子的假定功能以及二者在动脉粥样硬化斑块中的高水平表达和共定位表明它们在斑块发病机制和稳定性中起重要作用。
