CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure.
CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure.
复制标题
巨噬细胞中 CD36 依赖性 7-酮胆固醇积累介导慢性空气污染暴露引起的动脉粥样硬化进展。
DOI：
10.1161/circresaha.115.304666
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发表时间：
2014-10-10
影响因子：
20.1
通讯作者：
Rajagopalan S
中科院分区：
文献类型：
--
作者：
Rao X;Zhong J;Maiseyeu A;Gopalakrishnan B;Villamena FA;Chen LC;Harkema JR;Sun Q;Rajagopalan S
空气污染暴露已被证明会增强人类和动物的斑块进展。我们以前的研究表明氧化脂质在介导空气污染对血管的不良影响中起作用。然而，对空气污染物的反应中形成的氧化脂质的类型以及这种情况如何发生及其与动脉粥样硬化的相关性尚未完全了解。探讨<2.5 μ m颗粒物（PM2.5）诱导动脉粥样硬化进展的机制。将易患动脉粥样硬化的ApoE −/−或LDLR −/−小鼠暴露于过滤空气或使用多功能气溶胶浓缩器富集系统浓缩的环境PM2.5中6个月。PM2.5增加7-酮胆固醇（7-KCh），胆固醇的氧化修饰形式，在血浆IDL/LDL组分和主动脉斑块伴随动脉粥样硬化的进展，并增加CD36表达的斑块巨噬细胞从PM2.5暴露的小鼠。从PM2.5暴露的小鼠分离的巨噬细胞显示氧化脂质的摄取增加，而不改变其外排能力。与这些发现一致，CD36阳性巨噬细胞显示出氧化脂质摄取能力增强。造血细胞上CD 36的缺乏减少了空气污染对7-KCh积累、泡沫细胞形成和动脉粥样硬化的影响。我们的研究结果表明，CD36介导的氧化脂质如7-KCh的异常积累在空气污染诱导的动脉粥样硬化进展中的潜在作用。
Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis is not fully understood. To investigate the mechanisms by which particulate matter< 2.5μm (PM2.5) induces progression of atherosclerosis. Atherosclerosis-prone ApoE−/− or LDLR−/− mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma IDL/LDL fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque-macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis. Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids such as 7-KCh in air pollution induced atherosclerosis progression.