The role of macrophage transcription factor MafB in atherosclerotic plaque stability

- Macrophage-specific MafB inhibition deteriorated atherosclerotic plaque stability.
- MafB inhibition did not affect atherosclerotic lesion area.
- MafB inhibition was susceptible to macrophage apoptosis induced by oxidative stress.
- MafB inhibition did not affect macrophage infiltration and efferocytosis.
- MafB inhibition augmented expression of MMP-9 and inflammatory mediators.

Background and aimsMacrophage differentiation is associated with the development of atherosclerosis and plaque vulnerability and is regulated by transcription factor MafB. We previously reported that MafB attenuates macrophage apoptosis, which is associated with atherosclerotic plaque instability. The aim of this study was to elucidate the role of MafB in the progression of atherosclerotic plaque.MethodsWe generated macrophage-specific dominant-negative (DN) MafB transgenic mice and intercrossed DN-MafB mice with apolipoprotein E (ApoE) knockout (KO) mice.ResultsThere was no significant difference in advanced atherosclerotic lesion area between DN-MafB/ApoE KO mice and littermate control ApoE KO mice 9 weeks after high-cholesterol diet. However, DN-MafB/ApoE KO mice showed significantly larger necrotic cores and lower collagen content in atherosclerotic plaques than ApoE KO mice. Although there was no difference in intraplaque macrophage infiltration and efferocytosis, DN-MafB/ApoE KO mice showed significantly more apoptotic macrophages at the plaque edges than did ApoE KO mice. Real-time PCR analysis revealed that peritoneal macrophages of DN-MafB/ApoE KO mice had a greater increase in matrix metalloproteinase-9 and mRNA expression of inflammatory/M1 macrophage markers (tissue necrosis factor-α, interleukin-6, CD11c, and p47phox) after lipopolysaccharide stimulation than those of ApoE KO mice.ConclusionMacrophage-specific inhibition of MafB may destabilize atherosclerotic plaques in advanced lesions.