Atherogenic Lipids and Lipoproteins Trigger CD36-TLR2-Dependent Apoptosis in Macrophages Undergoing Endoplasmic Reticulum Stress

被引：517

作者：

Seimon, Tracie A. ^{[1
]}

Nadolski, Marissa J. ^{[1
]}

Liao, Xianghai ^{[1
]}

Magallon, Jorge ^{[1
]}

Nguyen, Matthew ^{[1
]}

Feric, Nicole T. ^{[4
]}

Koschinsky, Marlys L. ^{[4
]}

Harkewicz, Richard ^{[5
,6
]}

Witztum, Joseph L. ^{[5
,6
]}

Tsimikas, Sotirios ^{[5
,6
]}

Golenbock, Douglas ^{[7
]}

Moore, Kathryn J. ^{[8
]}

Tabas, Ira ^{[1
,2
,3
]}

机构：

[1] Columbia Univ, Dept Med, New York, NY 10032 USA

[2] Columbia Univ, Dept Anat & Cell Biol, New York, NY 10032 USA

[3] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA

[4] Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada

[5] Univ Calif San Diego, Div Endocrinol & Metab, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Div Cardiol, La Jolla, CA 92093 USA

[7] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA

[8] NYU, Sch Med, Leon H Charney Div Cardiol, Marc & Ruti Bell Program Vasc Biol & Dis, New York, NY 10016 USA

来源：

CELL METABOLISM | 2010年 / 12卷 / 05期

关键词：

TOLL-LIKE RECEPTOR-2; LOW-DENSITY-LIPOPROTEIN; E-DEFICIENT MICE; ADVANCED ATHEROSCLEROTIC LESIONS; INDUCED INSULIN-RESISTANCE; UNFOLDED PROTEIN RESPONSE; SMOOTH-MUSCLE-CELLS; SCAVENGER RECEPTOR; APOLIPOPROTEIN-E; CUTTING EDGE;

D O I：

10.1016/j.cmet.2010.09.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Macrophage apoptosis in advanced atheromata, a key process in plaque necrosis, involves the combination of ER stress with other proapoptotic stimuli. We show here that oxidized phospholipids, oxidized LDL, saturated fatty acids (SFAs), and lipoprotein(a) trigger apoptosis in ER-stressed macrophages through a mechanism requiring both CD36 and Toll-like receptor 2 (TLR2). In vivo, macrophage apoptosis was induced in SFA-fed, ER-stressed wildtype but not Cd36(-/-) or Tlr2(-/-) mice. For atherosclerosis, we combined TLR2 deficiency with that of TLR4, which can also promote apoptosis in ER-stressed macrophages. Advanced lesions of fat-fed Ldlr(-/-) mice transplanted with Tlr4(-/-)Tlr2(-/-) bone marrow were markedly protected from macrophage apoptosis and plaque necrosis compared with WT -> Ldlr(-/-) lesions. These findings provide insight into how atherogenic lipoproteins trigger macrophage apoptosis in the setting of ER stress and how TLR activation might promote macrophage apoptosis and plaque necrosis in advanced atherosclerosis.

引用

页码：467 / 482

页数：16

共 76 条

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Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].