Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
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DOI：
10.1172/jci29950
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发表时间：
2007-01-01
影响因子：
15.9
通讯作者：
Pittet, Milkael J.
中科院分区：
文献类型：
--
作者：
Swirski, Filip K.;Libby, Peter;Pittet, Milkael J.
巨噬细胞聚集决定性地参与动脉粥样硬化的发展和恶化。循环单核细胞，巨噬细胞的前体，在小鼠和人类中显示异质性，但它们对动脉粥样硬化形成的相对贡献仍然未知。我们在此报道，在高胆固醇血症apoE缺陷小鼠中，Ly-6C（hi）单核细胞亚群显著增加，每月血液中Ly-6C（hi）细胞的数量增加一倍。Ly-6C（hi）单核细胞粘附于活化的内皮，浸润病变，并成为病变巨噬细胞。高胆固醇血症相关单核细胞增多症（HAM）是由于存活率增加、细胞持续增殖以及Ly-6C（hi）向Ly-6C（lo）转化受损而发展起来的，并在他汀类药物诱导的胆固醇降低后消退。相反，Ly-6C（lo）细胞的数量保持不受影响。因此，我们认为Ly-6C（hi）单核细胞代表了实验性动脉粥样硬化中炎症反应的一个新认识的组成部分。
Macrophage accumulation participates decisively in the development and exacerbation of atherosclerosis. Circulating monocytes, the precursors of macrophages, display heterogeneity in mice and humans, but their relative contribution to atherogenesis remains unknown. We report here that the Ly-6C(hi) monocyte subset increased dramatically in hypercholesterolemic apoE-deficient mice consuming a high-fat diet, with the number of Ly-6C(hi) cells doubling in the blood every month. Ly-6C(hi) monocytes adhered to activated endothelium, infiltrated lesions, and became lesional macrophages. Hypercholesterolemia-associated monocytosis (HAM) developed from increased survival, continued cell proliferation, and impaired Ly-6C(hi) to Ly-6C(lo) conversion and subsided upon statin-induced cholesterol reduction. Conversely, the number of Ly-6C(lo) cells remained unaffected. Thus, we believe that Ly-6C(hi) monocytes represent a newly recognized component of the inflammatory response in experimental atherosclerosis.