Abstract 13866: Inhibition of Macrophage Transcriptional Factor Mafb Exacerbates Atherosclerotic Plaque Vulnerability
It is well known that the monocyte/macrophage has a crucial role in the development of atherosclerosis. Macrophage differentiation is also acknowledged as critical for the development of atherosclerosis. Transcriptional factor MafB is associated with macrophage differentiation. We previously showed that MafB attenuates macrophage apoptosis, which is associated with atherosclerotic plaque instability. The aim of this study was to elucidate a role of MafB in progression of atherosclerotic plaque. We generated macrophage specific dominant negative (DN) MafB transgenic mice and DN-MafB/ApoE knockout (KO) mice. There was no difference in advanced atherosclerotic lesion area between ApoE KO mice and DN-MafB/ApoE KO mice 9 weeks after high-cholesterol diet. However, DN-MafB/ApoE KO mice had significantly larger necrotic cores and more decreased collagen content in atherosclerotic plaques than ApoE KO mice. Although there was no difference in macrophage content in atherosclerotic plaques, DN-MafB/ApoE KO mice showed significantly larger number of apoptotic macrophages at plaque sites than ApoE KO mice. Real time PCR analysis revealed that peritoneal macrophages of DN-MafB/ApoE KO mice had a greater increase in mRNA expression of inflammatory/M1 macrophage markers (IL-6, TNF-α, CD11c, p22phox, and p47phox) after stimulation of LPS than those of ApoE KO mice. Dihydroethidium staining showed that production of reactive oxygen species in atherosclerotic plaque lesions was higher in DN-MafB/ApoE KO mice than in ApoE KO mice.In conclusions, macrophage-specific inhibition of MafB may exacerbate plaque instability in advanced atherosclerotic lesion.
- © 2012 by American Heart Association, Inc.