A role for the apoptosis inhibitory factor AIM/Spα/Api6 in atherosclerosis development

被引:261
作者
Arai, S
Shelton, JM
Chen, MY
Bradley, MN
Castrillo, A
Bookout, AL
Mak, PA
Edwards, PA
Mangelsdorf, DJ
Tontonoz, P
Miyazaki, T
机构
[1] Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA
[3] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA
[4] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA
[5] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Dept Biol Chem & Med, Los Angeles, CA 90095 USA
关键词
D O I
10.1016/j.cmet.2005.02.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Macrophages play a central role in the development of atherosclerosis through the accumulation of oxidized LDL (oxLDL). AIM (Sp alpha/Api6) has previously been shown to promote macrophage survival; however, its function in atherogenesis is unknown. Here we identify AIM as a critical factor that protects macrophages from the apoptotic effects of oxidized lipids. AIM protein is induced in response to oxLDL loading and is highly expressed in foam cells within atherosclerotic lesions. Interestingly, both expression of AIM in lesions and its induction by oxidized lipids require the action of LXR/RXR heterodimers. AIM(-/-) macrophages are highly susceptible to oxLDL-induced apoptosis in vitro and undergo accelerated apoptosis in atherosclerotic lesions in vivo. Moreover, early atherosclerotic lesions in AIM(-/-)LDLR(-/-) double knockout mice are dramatically reduced when compared to AIM(+/+)LDLR(-/-) controls. We conclude that AIM production facilitates macrophage survival within atherosclerotic lesions and that loss of AIM decreases early lesion development by increasing macrophage apoptosis.
引用
收藏
页码:201 / 213
页数:13
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