Brief Report: Increased Apoptosis in Advanced Atherosclerotic Lesions of Apoe −/− Mice Lacking Macrophage Bcl-2

Abstract

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— Bcl2 flox -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 Bcl2 WT -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, Bcl2 flox -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 Bcl2 WT -LysMCre lesions. Conclusions— Macrophage Bcl-2 plays a protective role against macrophage apoptosis specifically in advanced atherosclerotic lesions of Apoe −/− mice.