MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B
MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B
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DOI：
10.1172/jci5624
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发表时间：
1999-03-01
影响因子：
15.9
通讯作者：
Charo, IF
中科院分区：
文献类型：
--
作者：
Gosling, J;Slaymaker, S;Charo, IF
最早可识别的动脉粥样硬化病变是由富含脂质的巨噬细胞（泡沫细胞）组成的脂肪条纹。循环单核细胞是这些泡沫细胞的前体，但人们对控制巨噬细胞通过血管壁运输的分子机制知之甚少。单核细胞趋化蛋白-1 (MCP-1) 是趋化因子（趋化细胞因子）家族的成员，是一种有效的单核细胞激动剂，可通过氧化脂质上调。最近对缺乏 apo E 或低密度脂蛋白受体的高胆固醇血症小鼠的研究表明，MCP-1 在单核细胞募集到早期动脉粥样硬化病变中发挥着作用。为了确定MCP-1是否在生理血浆胆固醇水平升高的情况下严重参与动脉粥样硬化形成，我们在表达人apo B的转基因小鼠中删除了MCP-1基因。在这里，我们报告说，MCP-1的缺失为apo B转基因小鼠提供了对巨噬细胞募集和动脉粥样硬化病变形成的显着保护，而不改变脂蛋白代谢。与早期研究的结果相结合，这些数据提供了令人信服的证据，证明 MCP-1 在动脉粥样硬化的引发中发挥着关键作用。
The earliest recognizable atherosclerotic lesions are fatty streaks composed of lipid-laden macrophages (foam cells). Circulating monocytes are the precursors of these foam cells, but the molecular mechanisms that govern macrophage trafficking through the vessel wall are poorly understood. Monocyte chemoattractant protein-1 (MCP-1), a member of the chemokine (chemotactic cytokine) family, is a potent monocyte agonist that is upregulated by oxidized lipids. Recent studies in hypercholesterolemic mice lacking apo E or the low-density lipoprotein receptor have suggested a role for MCP-1 in monocyte recruitment to early atherosclerotic lesions. To determine if MCP-1 is critically involved in atherogenesis in the setting of elevated physiological plasma cholesterol levels, we deleted the MCP-1 gene in transgenic mice expressing human apo B. Here we report that the absence of MCP-1 provides dramatic protection from macrophage recruitment and atherosclerotic lesion formation in apo B transgenic mice, without altering lipoprotein metabolism. Taken together with the results of earlier studies, these data provide compelling evidence that MCP-1 plays a critical role in the initiation of atherosclerosis.