Brief report: Increased apoptosis in advanced atherosclerotic lesions of Apoe^-/- mice lacking macrophage Bcl-2

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 Bcl _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_WTLysMCre lesions. Conclusions-Macrophage Bcl-2 plays a protective role against macrophage apoptosis specifically in advanced atherosclerotic lesions of Apoe^-/- mice.