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

Satoko Arai, John M. Shelton, Mingyi Chen, Michelle N. Bradley, Antonio Castrillo, Angie L. Bookout, Puiying A. Mak, Peter A. Edwards, David J. Mangelsdorf, Peter Tontonoz, Toru Miyazaki

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

Macrophages play a central role in the development of atherosclerosis through the accumulation of oxidized LDL (oxLDL). AIM (Spα/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.

Original languageEnglish (US)
Pages (from-to)201-213
Number of pages13
JournalCell Metabolism
Volume1
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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    Arai, S., Shelton, J. M., Chen, M., Bradley, M. N., Castrillo, A., Bookout, A. L., Mak, P. A., Edwards, P. A., Mangelsdorf, D. J., Tontonoz, P., & Miyazaki, T. (2005). A role for the apoptosis inhibitory factor AIM/Spα/Api6 in atherosclerosis development. Cell Metabolism, 1(3), 201-213. https://doi.org/10.1016/j.cmet.2005.02.002