Ström Asa, Franzén Ahnders, Wängnerud Christel, Knutsson Ann-Katrin, Heinegård Dick, Hultgårdh-Nilsson Anna
Department of Cell and Molecular Biology, Section for Connective Tissue Biology, Lund University, Lund, Sweden.
J Vasc Res. 2004 Jul-Aug;41(4):314-22. doi: 10.1159/000079205. Epub 2004 Jun 21.
Osteopontin (OPN) is a cell-binding phosphoprotein with proposed functions in atherosclerosis. The aim of this study was to examine how OPN deficiency affects the atherosclerotic process.
ApoE/LDL receptor/OPN triple knockout (ALO) mice were generated by crossing OPN null mice with ApoE/LDL receptor-deficient (AL) mice. Analysis were made on tissue sections from the aortic arch of 8-, 20- and 34-week female AL and ALO mice and included morphometric measurements, collagen staining, TUNEL staining and immunohistochemistry with antibodies to OPN, macrophages and proliferating cellular nuclear antigen (PCNA).
Lesion and media areas were significantly smaller and collagen accumulation in lesions was significantly reduced in 34-week-old ALO mice compared with AL mice. The numbers of proliferating and apoptotic cells were increased in lesions of 34 weeks old ALO mice. Furthermore, the plasma levels of SAA and total cholesterol were significantly decreased in 34 weeks old ALO mice.
The present study shows that OPN deficiency reduces atherogenesis in atherosclerotic mice. The results corroborate and extend recently published findings and also include novel data on the role of OPN in the process of remodeling, inflammation and lipid metabolism.
骨桥蛋白（OPN）是一种细胞结合磷蛋白，在动脉粥样硬化中具有多种潜在功能。本研究旨在探讨OPN缺乏如何影响动脉粥样硬化进程。
通过将OPN基因敲除小鼠与载脂蛋白E/低密度脂蛋白受体缺陷（AL）小鼠杂交，培育出载脂蛋白E/低密度脂蛋白受体/OPN三基因敲除（ALO）小鼠。对8周龄、20周龄和34周龄雌性AL和ALO小鼠主动脉弓的组织切片进行分析，包括形态测量、胶原染色、TUNEL染色以及使用抗OPN、巨噬细胞和增殖细胞核抗原（PCNA）抗体进行免疫组织化学分析。
与AL小鼠相比，34周龄ALO小鼠的病变面积和中膜面积显著减小，病变中的胶原积累显著减少。34周龄ALO小鼠病变中增殖细胞和凋亡细胞的数量增加。此外，34周龄ALO小鼠的血清淀粉样蛋白A（SAA）和总胆固醇血浆水平显著降低。
本研究表明，OPN缺乏可减轻动脉粥样硬化小鼠的动脉粥样硬化形成。这些结果证实并扩展了最近发表的研究结果，还包括了关于OPN在重塑、炎症和脂质代谢过程中作用的新数据。
