Ly-6Chi Monocytes Dominate Hypercholesterolemia-associated Monocytosis and Give Rise to Macrophages in Atheromata

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2007 Jan 4

PMID 17200719

Citations 647

Authors

Filip K Swirski

Peter Libby

Elena Aikawa

Pilar Alcaide

F William Luscinskas

Ralph Weissleder

Mikael J Pittet

Affiliations

Soon will be listed here.

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-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.

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