@article{1dc7aad5031646f0b304de940934e2fa,
title = "A role for the apoptosis inhibitory factor AIM/Spα/Api6 in atherosclerosis development",
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.",
author = "Satoko Arai and Shelton, {John M.} and Mingyi Chen and Bradley, {Michelle N.} and Antonio Castrillo and Bookout, {Angie L.} and Mak, {Puiying A.} and Edwards, {Peter A.} and Mangelsdorf, {David J.} and Peter Tontonoz and Toru Miyazaki",
note = "Funding Information: We thank Drs D. Russell, H. Hobbs, J. Herz (Dallas), D. Mathis, and M. Shimada (Boston) for helpful advice and critical reading of manuscript; Dr. S. Ohnishi (Tokyo) for help in cholesterol profiling; the core histology facility at UTSW (Dallas) and Dr. K. Miyake (Dallas) for technical assistance; Dr. T. Kadowaki (Tokyo) for the kind gift of LG100153; and Dr. T. Willson (GlaxoSmithKline) for GW3965. We also appreciate Dr. E.K. Wakeland (Dallas) for his kind advice about the genetic analysis of mice; S. Subramanian and G. Westerfield (Dallas) for the help in preparing the manuscript. T.M. is supported by grants of NIH (RO1-AI050948A2, R21-AI050948), JDRF (1-2001-581), ALF, PAF, and HHMI. D.J.M. and P.T. are investigators of the Howard Hughes Medical Institute. P.T. is also supported by NIH grants (HL66088 and HL30568), and P.A.E. is supported by an NIH grant (HL 30568). None of the authors have a financial interest related to this work.",
year = "2005",
month = mar,
doi = "10.1016/j.cmet.2005.02.002",
language = "English (US)",
volume = "1",
pages = "201--213",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}