Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
Filip K. Swirski, Peter Libby, Elena Aikawa, Pilar Alcaide, F. William Luscinskas, Ralph Weissleder, Mikael J. Pittet
Filip K. Swirski, Peter Libby, Elena Aikawa, Pilar Alcaide, F. William Luscinskas, Ralph Weissleder, Mikael J. Pittet
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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 6

Statin treatment limits monocytosis.

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Statin treatment limits monocytosis. apoE–/– mice consumed Western diet ...
apoE–/– mice consumed Western diet supplemented or not with atorvastatin for 25 weeks. A control group of apoE–/– mice received regular chow. (A) Serum cholesterol after 25 weeks of diet. (B) Number of leukocytes, monocytes, and Ly-6Chi and Ly-6Clo subtypes in bone marrow, blood, and spleen. (C) Association between serum cholesterol and number of circulating Ly-6Chi or Ly-6Clo monocytes after 25 weeks of diet. Mean ± SEM are shown for apoE–/– mice on chow (filled circles), Western diet (open circles), and Western diet supplemented with atorvastatin (gray circles). Results are pooled from 9 independent experiments (n = 3–14 per group). Student’s t test was used.