The role of macrophage transcription factor MafB in atherosclerotic plaque stability

Atherosclerosis. 2016 Jul:250:133-43. doi: 10.1016/j.atherosclerosis.2016.05.021. Epub 2016 May 14.

Abstract

Background and aims: Macrophage 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.

Methods: We generated macrophage-specific dominant-negative (DN) MafB transgenic mice and intercrossed DN-MafB mice with apolipoprotein E (ApoE) knockout (KO) mice.

Results: There 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.

Conclusion: Macrophage-specific inhibition of MafB may destabilize atherosclerotic plaques in advanced lesions.

Keywords: Apoptosis; Macrophage; MafB; Plaque stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Atherosclerosis / pathology
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Female
  • Inflammation
  • Interleukin-6 / metabolism
  • Macrophages / metabolism*
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / physiology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Mice, Transgenic
  • Oxidative Stress*
  • Plaque, Atherosclerotic / metabolism*
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • MafB Transcription Factor
  • Mafb protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse