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Brief Review |
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.
Correspondence to Ira Tabas, MD, PhD, Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032. 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
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Arterioscler Thromb Vasc Biol 2009 29: 153-155.
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