Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice
Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice
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DOI：
10.1161/01.atv.0000074878.29805.d0
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发表时间：
2003-06-01
影响因子：
8.7
通讯作者：
Uede, T
中科院分区：
文献类型：
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作者：
Matsui, Y;Rittling, SR;Uede, T
骨桥蛋白（OPN）是一种非胶原粘附蛋白，与动脉粥样硬化有关，其中动脉粥样硬化斑块内的巨噬细胞表达OPN。然而，目前尚不清楚OPN表达的升高是否是动脉粥样硬化的原因或结果。方法和结果-我们产生了缺乏OPN的小鼠，并将其与载脂蛋白（apo）E缺陷小鼠杂交，并在正常饮食36周后用混合C57 BL/6x 129背景分析这些小鼠。在雌性小鼠中，与OP+/+E-/-小鼠相比，OP+/-E-/-和OP-/-E-/-小鼠的动脉粥样硬化和炎性病变明显较小，这反映在MOMA-2阳性染色面积较小。而在雄性小鼠中，3种基因型的动脉粥样硬化病变面积无显著差异。在OP-/-E-/-和OP+/+E-/-小鼠中，检测到典型的动脉粥样硬化病变，包括坏死核心、泡沫细胞聚集和胆固醇裂隙。然而，我们发现，在60周龄的雄性OP-/-E-/-小鼠的血管矿物质沉积面积显着增加相比，在OP+/+E-/- male mice. Conclusions-这些结果表明，OPN在动脉粥样硬化和抑制血管钙化中发挥促进作用。女性中OPN表达的抑制应该被认为是动脉粥样硬化的治疗可能性。
Objective-Osteopontin (OPN), a noncollagenous adhesive protein, is implicated in atherosclerosis, in which macrophages within atherosclerotic plaques express OPN. However, it is not known whether the elevated OPN expression is a cause or result of atherosclerosis.Methods and Results-We generated mice that lacked OPN and crossed them with apolipoprotein (apo) E-deficient mice and analyzed these mice with a mixed C57BL/6x129 background after 36 weeks on a normal chow diet. In female mice, OP+/-E-/- and OP-/-E-/- mice had significantly smaller atherosclerotic and inflammatory lesions compared with OP+/+E-/- mice, and that was reflected by smaller area of MOMA-2-positive staining. In male mice, however, there was no significant difference in the atherosclerosis lesion areas among 3 genotypes. In both OP-/-E-/- and OP+/+E-/- mice, typical atherosclerotic lesions were detected, which include necrotic core, foamy cell collections, and cholesterol clefts. However, we found that vascular mineral-deposited areas in 60-week-old male OP-/-E-/- mice were significantly increased compared with those in OP+/+E-/- male mice.Conclusions-These results suggest that OPN plays a promoting effect in atherosclerosis and inhibitory effect in vascular calcification. The suppression of OPN expression in females should be considered a therapeutic possibility in atherosclerosis.