Local proliferation dominates lesional macrophage accumulation in atherosclerosis (Nat Med. 2013 Sep;19(9):1166-72.)

報告日期: 2014/05/23
報告時間: 5:10/6:00
報告學生: 賴弘岳(以英文報告)
講評老師: 葉才明
附件下載: 下載[1413-1396957735-1.pdf] 

Localproliferationdominateslesionalmacrophageaccumulation in atherosclerosis

Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y, Figueiredo JL, Gorbatov R, Sukhova GK, Gerhardt LM, Smyth D, Zavitz CC, Shikatani EA, Parsons M, van Rooijen N, Lin HY, Husain M, Libby P, Nahrendorf M, Weissleder R, Swirski FK

Nat Med. 2013 Sep;19(9):1166-72

SpeakerLai Hong-Yue                                 Date2014/05/23  17:10-18:00

CommentatorDr. Yeh Trai-Ming                                    PlaceRoom 602

 

Abstract

It has long been evident that macrophages are a major component of atherosclerotic plaques. During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall. Engorged with cholesterol, macrophages cause plaques to bulk up, leading to the narrowing of arteries, and they promote plaque rupture. Accordingly, unraveling how macrophage accu­mulation in plaques occurs is crucial to under­standing how atherosclerotic lesions develop and discovering potential points of therapeu­tic intervention.It has been widely assumed that therate-limiting event in the accumulation of macrophages during the progression of the disease isthe recruitment of circulating monocytes.Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts. The authors therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis.In murine atherosclerotic lesions, they found that macrophages turn over rapidly, after 4 weeks. The key experimental approach of the study used a technique called parabiosis. In parabiosis, two living mice are joinedtogether surgically so that they sharea circulatory system.Because blood cells are exchanged between the parabionts, the method has broad utility in mapping the fates of cells potentially derived from circulating precursors. 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). Their study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease.

 

References

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