Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata

被引：1041

作者：

Swirski, Filip K.

Libby, Peter

Aikawa, Elena

Alcaide, Pilar

Luscinskas, F. William

Weissleder, Ralph

Pittet, Milkael J.

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA

[2] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Dept Pathol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2007年 / 117卷 / 01期

关键词：

D O I：

10.1172/JCI29950

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：195 / 205

页数：11

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