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 approximately 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.