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.


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.
Thorp
Edward
E
Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Li
Yankun
Y
Bao
Liping
L
Yao
Pin Mei
PM
Kuriakose
George
G
Rong
James
J
Fisher
Edward A
EA
Tabas
Ira
I
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2
D001057:Apolipoproteins E; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse