Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
Filip K. Swirski, … , Ralph Weissleder, Mikael J. Pittet
Filip K. Swirski, … , Ralph Weissleder, Mikael J. Pittet
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):195-205. https://doi.org/10.1172/JCI29950.
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Research Article

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

Abstract

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-6Chi monocyte subset increased dramatically in hypercholesterolemic apoE–deficient mice consuming a high-fat diet, with the number of Ly-6Chi cells doubling in the blood every month. Ly-6Chi 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-6Chi to Ly-6Clo conversion and subsided upon statin-induced cholesterol reduction. Conversely, the number of Ly-6Clo cells remained unaffected. Thus, we believe that Ly-6Chi monocytes represent a newly recognized component of the inflammatory response in experimental atherosclerosis.

Authors

Filip K. Swirski, Peter Libby, Elena Aikawa, Pilar Alcaide, F. William Luscinskas, Ralph Weissleder, Mikael J. Pittet

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Figure 4

Atherosclerotic lesions contain Ly-6Chi monocytes.

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Atherosclerotic lesions contain Ly-6Chi monocytes. (A) A...
(A) Aortas from apoE+/+ and apoE–/– mice on chow and Western diet were digested with a protease cocktail. Cells were dispersed and stained with anti-CD11b, -CD90, -B220, -CD49b, -NK1.1, –Ly-6G, -F4/80, –I-Ab, -CD11c, and –Ly-6C mAb. Percent (mean ± SEM) are shown for each quadrant. (B) Number of retrieved Ly-6Chi and Ly-6Clo monocytes per aorta in apoE+/+ and apoE–/– mice on chow and Western diet. Results are pooled from 5 independent experiments with 2–5 mice per group. Mean and SEM are shown. #P < 0.001 versus all other groups (1-way ANOVA with Tukey’s multiple comparison test). (C) Immunohistochemistry depicts the intima at the aortic root of a representative apoE–/– mouse on Western diet and an apoE+/+ mouse on chow. Sections stained with anti-CD31, –Ly-6C, and –Mac-3 mAbs are shown. Original magnification, ×400.