Local proliferation dominates lesional macrophage accumulation in atherosclerosis

被引：840

作者：

Robbins, Clinton S. ^{[1
,2
,3
,4
,5
]}

Hilgendorf, Ingo ^{[1
,2
]}

Weber, Georg F. ^{[1
,2
]}

Theurl, Igor ^{[1
,2
]}

Iwamoto, Yoshiko ^{[1
,2
]}

Figueiredo, Jose-Luiz ^{[1
,2
,6
]}

Gorbatov, Rostic ^{[1
,2
]}

Sukhova, Galina K. ^{[6
]}

Gerhardt, Louisa M. S. ^{[1
,2
]}

Smyth, David ^{[3
]}

Zavitz, Caleb C. J. ^{[3
]}

Shikatani, Eric A. ^{[3
,4
]}

Parsons, Michael ^{[7
]}

van Rooijen, Nico ^{[8
]}

Lin, Herbert Y. ^{[1
,2
]}

Husain, Mansoor ^{[3
,4
]}

Libby, Peter ^{[6
]}

Nahrendorf, Matthias ^{[1
,2
]}

Weissleder, Ralph ^{[1
,2
,9
]}

Swirski, Filip K. ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada

[4] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[5] Univ Toronto, Dept Immunol, Toronto, ON, Canada

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

[7] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[8] Free Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands

[9] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA

来源：

NATURE MEDICINE | 2013年 / 19卷 / 09期

基金：

美国国家卫生研究院;

关键词：

HEMATOPOIETIC PROGENITOR CELLS; MONOCYTE ACCUMULATION; MYOCARDIAL-INFARCTION; IN-VIVO; RECRUITMENT; PATTERN; MICE; ENHANCEMENT; CX3CR1; BLOOD;

D O I：

10.1038/nm.3258

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall(1,2). 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 contexts(10). 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.

引用

页码：1166 / 1172

页数：7

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