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A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development.
Satoko Arai1, John M Shelton, Mingyi Chen
1Center for Immunology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard NA7200, Dallas, Texas 75390, USA.
Cell Metabolism
|August 2, 2005
Summary
AIM protein protects macrophages from oxidized lipids, a key factor in atherosclerosis. Loss of AIM increases macrophage apoptosis, reducing early lesion development in mice.
Area of Science:
- Cardiovascular Biology
- Immunology
- Lipid Metabolism
Background:
- Macrophages are central to atherosclerosis development, accumulating oxidized LDL (oxLDL).
- AIM (Spalpha/Api6) promotes macrophage survival, but its role in atherogenesis is unclear.
Purpose of the Study:
- To investigate the function of AIM in macrophage response to oxidized lipids and its role in atherosclerosis.
Main Methods:
- Assessing AIM expression in macrophages exposed to oxLDL.
- Analyzing AIM's role in oxLDL-induced apoptosis in AIM-/- macrophages.
- Evaluating atherosclerosis development in AIM-/-LDLR-/- double knockout mice.
Main Results:
- AIM protein is induced by oxLDL and highly expressed in atherosclerotic foam cells.
- AIM induction by oxLDL requires LXR/RXR heterodimers.
- AIM-/- macrophages exhibit increased susceptibility to oxLDL-induced apoptosis.
- AIM deficiency significantly reduces early atherosclerotic lesion development in mice.
Conclusions:
- AIM is a critical factor protecting macrophages from oxidized lipid-induced apoptosis.
- AIM facilitates macrophage survival within atherosclerotic lesions.
- Loss of AIM exacerbates macrophage apoptosis, thereby decreasing early lesion progression.