Local proliferation dominates lesional macrophage accumulation in atherosclerosis

Clinton S. Robbins, Ingo Hilgendorf, Georg F. Weber, Igor Theurl, Yoshiko Iwamoto, Jose Luiz Figueiredo, Rostic Gorbatov, Galina K. Sukhova, Louisa M.S. Gerhardt, David Smyth, Caleb C.J. Zavitz, Eric A. Shikatani, Michael Parsons, Nico Van Rooijen, Herbert Y. Lin, Mansoor Husain, Peter Libby, Matthias Nahrendorf, Ralph Weissleder, Filip K. Swirski

Research output: Contribution to journalArticlepeer-review

817 Scopus citations

Abstract

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall1,2. The observation that circulating monocytes give rise to lesional macrophages 3-9 has reinforced the concept that monocyte infiltration dictates macrophage buildup. Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts10. We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (SR-A). Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease.

Original languageEnglish
Pages (from-to)1166-1172
Number of pages7
JournalNature Medicine
Volume19
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

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