Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice
Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice
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DOI：
10.1172/jci9259
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发表时间：
2000-04-01
影响因子：
15.9
通讯作者：
Silverstein, RL
中科院分区：
文献类型：
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作者：
Febbraio, M;Podrez, EA;Silverstein, RL
巨噬细胞清道夫受体在动脉粥样硬化的发病机制中起着关键作用。为了评估B类清道夫受体CD 36在动脉粥样硬化形成中的作用，我们将CD 35-null菌株与致动脉粥样硬化的载脂蛋白E-null菌株杂交，并量化病变的发展。与对照组相比，CD 36-apo E双敲除小鼠的主动脉树病变面积（西方饮食）减少76.5%，主动脉窦病变面积（正常食物）减少45%，尽管脂蛋白谱的改变通常与动脉粥样硬化性增加相关。来自CD 36-apo E双缺失小鼠的巨噬细胞结合和内化的铜氧化LDL和由单核细胞产生的活性氮物质修饰的LDL减少了60%以上。观察到暴露于这些配体后对体外脂质蓄积和泡沫细胞形成的类似抑制。这些结果支持了CD 36在体内动脉粥样硬化病变发展中的重要作用，并表明阻断CD 36即使在更极端的致动脉粥样硬化情况下也具有保护作用。
Macrophage scavenger receptors have been implicated as key players in the pathogenesis of atherosclerosis. To assess the role of the class B scavenger receptor CD36 in atherogenesis, we crossed a CD35-null strain with the atherogenic apo E-null strain and quantified lesion development. There was a 76.5% decrease in aortic tree lesion area (Western diet) and a 45% decrease in aortic sinus lesion area (normal chow) in the CD36-apo E double-null mice when compared with controls, despite alterations in lipoprotein profiles that often correlate with increased atherogenicity. Macrophages derived from CD36-apo E double-null mice bound and internalized more than 60% less copper-oxidized LDL and LDL modified by monocyte-generated reactive nitrogen species. A similar inhibition of in vitro lipid accumulation and foam cell formation after exposure to these Ligands was seen. These results support a major role for CD36 in atherosclerotic lesion development in vivo and suggest that blockade of CD36 can be protective even in more extreme proatherogenic circumstances.