on November 6, 2008
Published online before print November 6, 2008, doi: 10.1161/ATVBAHA.108.176495
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Submitted on February 16, 2008
Accepted on October 21, 2008
Increased Apoptosis in Advanced Atherosclerotic Lesions of Apoe-/- Mice Lacking Macrophage Bcl-2
Edward Thorp ;
From the Departments of Medicine (Y.L., L.B., E.T., G.K., I.T.), Pathology & Cell Biology (I.T.), and Physiology & Cellular Biophysics (I.T.), Columbia University, New York; and the Department of Medicine (J.R., E.A.F.), Leon Charney Division of Cardiology, New York University School of Medicine, New York.
* To whom correspondence should be addressed. E-mail: iat1{at}columbia.edu.
Objective—Macrophage apoptosis plays important roles in atherosclerosis. Bcl-2 is a key cell survival molecule, but its role in macrophage apoptosis in atherosclerosis is not known. The goal herein was to determine the effect of macrophage-targeted deletion of Bcl-2 on macrophage apoptosis in atherosclerotic lesions of Apoe-/- mice.
Methods and Results—Bcl2flox-LysMCre mice were created as a model of macrophage Bcl-2 deficiency. Macrophages from these mice were more susceptible to apoptosis than those from control Bcl2WT-LysMCre mice. The mice were bred onto the Apoe-/- background and fed a Western-type diet for 4 or 10 weeks. Apoptotic cells were equally very rare in the lesions of both groups of the 4-week-diet mice, and there was no difference in lesion area. However, Bcl2flox-LysMCre;Apoe-/- plaques from the 10-week-diet protocol had a 40% to 45% increase in apoptotic cells and, in female mice, a 
25% increase in plaque necrosis (P<0.05) compared with Bcl2WT-LysMCre lesions.
Conclusions—Macrophage Bcl-2 plays a protective role against macrophage apoptosis specifically in advanced atherosclerotic lesions of Apoe-/- mice.
Key words: atherosclerosis-pathophysiology • apoptosis • macrophage • animal models of human disease
Related Article:
- Cause or Consequence: What Does Macrophage Apoptosis Do in Atherosclerosis?
- Murray C.H. Clarke and Martin R. Bennett
Arterioscler Thromb Vasc Biol 2009 29: 153-155.[Extract] [Full Text] [PDF]
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