Publication
Title
Macrophage deficiency of MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice
Author
Abstract
ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stressinduced apoptosis may affect advanced atherosclerosis. Here we placed Apoe/ mice deficient in macrophage p38α MAPK on a Western diet and found that they had a marked increase in macrophage apoptosis and plaque necrosis. The macrophage p38αdeficient lesions also exhibited a significant reduction in collagen content and a marked thinning of the fibrous cap, which suggests that plaque progression was advanced in these mice. Consistent with our in vivo data, we found that ER stressinduced apoptosis in cultured primary mouse macrophages was markedly accelerated under conditions of p38 inhibition. Pharmacological inhibition or genetic ablation of p38 suppressed activation of Akt in cultured macrophages and in atherosclerotic lesions. In addition, inhibition of Akt enhanced ER stressinduced macrophage apoptosis, and expression of a constitutively active myristoylated Akt blocked the enhancement of ER stressinduced apoptosis that occurred with p38 inhibition in cultured cells. Our results demonstrate that p38α MAPK may play a critical role in suppressing ER stressinduced macrophage apoptosis in vitro and advanced lesional macrophage apoptosis in vivo.
Language
English
Source (journal)
The journal of clinical investigation. - New York, N.Y., 1924, currens
Publication
New York, N.Y. : 2009
ISSN
0021-9738 [print]
1558-8238 [online]
Volume/pages
119:4(2009), p. 886-898
ISI
000264830100026
Full text (Publishers DOI)
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 12.01.2012
Last edited 27.05.2017