References
Query Results -- Details
MGI Accession ID: MGI:3770239
J Number: J:129845
Other Accession IDs:
Title: A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development.
Authors: Arai S; Shelton JM; Chen M; Bradley MN; Castrillo A; Bookout AL; Mak PA; Edwards PA; Mangelsdorf DJ; Tontonoz P; Miyazaki T
Journal: Cell Metab
Volume: 1
Issue: 3
Date: 2005 Mar
Year: 2005
Pages: 201-13
Review Status: Peer Reviewed
Abstract:
Macrophages play a central role in the development of atherosclerosis through the accumulation of oxidized LDL (oxLDL). AIM (Spalpha/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.
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