Yu X, Dluz S, Graves D T, Zhang L, Antoniades H N, Hollander W, Prusty S, Valente A J, Schwartz C J, Sonenshein G E
Department of Oral Biology, Boston University Medical Center, MA 02118.
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6953-7. doi: 10.1073/pnas.89.15.6953.
Atherosclerosis is marked by an overt inflammatory infiltrate, with enhanced recruitment of monocytes/macrophages observed in both human and experimental atherosclerosis. We previously determined that monocyte chemoattractant protein 1 (MCP-1) accounts for virtually all of the chemotactic activity produced by vascular (aortic) smooth muscle cells in culture. We now report that arteries from a primate model of atherosclerosis with dietary-induced hypercholesterolemia exhibit increased levels of MCP-1 mRNA expression in vivo, whereas their normal counterparts demonstrate minimal MCP-1 expression. Furthermore, immunohistochemistry and in situ hybridization clearly indicate that the expression of MCP-1 protein and mRNA is in the smooth muscle cells of the medial layer of the artery and in monocyte-like and smooth muscle-like cells found in the overlying intimal lesion. These studies indicate that one of the responses to dietary hypercholesterolemia is the expression of MCP-1 by vascular smooth muscle cells. This expression, when augmented with other cellular and molecular factors, could significantly contribute to the recruitment of monocytes/macrophages to the vessel wall.
动脉粥样硬化的特征是有明显的炎症浸润，在人类和实验性动脉粥样硬化中均观察到单核细胞/巨噬细胞的募集增加。我们之前确定单核细胞趋化蛋白1（MCP-1）几乎占培养的血管（主动脉）平滑肌细胞产生的所有趋化活性。我们现在报告，在饮食诱导的高胆固醇血症的灵长类动物动脉粥样硬化模型中，体内动脉中MCP-1 mRNA表达水平升高，而正常对照动脉中MCP-1表达极少。此外，免疫组织化学和原位杂交清楚地表明，MCP-1蛋白和mRNA的表达位于动脉中层的平滑肌细胞以及在上覆内膜病变中发现的单核细胞样和平滑肌样细胞中。这些研究表明，饮食性高胆固醇血症的反应之一是血管平滑肌细胞表达MCP-1。这种表达，当与其他细胞和分子因素一起增强时，可能会显著促进单核细胞/巨噬细胞募集到血管壁。
