title: The role of macrophage transcription factor MafB in atherosclerotic plaque stability.
abstract: 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.
  
  
  
  We generated macrophage-specific dominant-negative (DN) MafB transgenic mice and intercrossed DN-MafB mice with apolipoprotein E (ApoE) knockout (KO) mice.
  
  
  
  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.
  
  
  
  Macrophage-specific inhibition of MafB may destabilize atherosclerotic plaques in advanced lesions.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan. Electronic address: tewatana@med.id.yamagata-u.ac.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Toshima
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Aida
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Nishiwaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Kadowaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Narumi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Otaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Netsu
authors.initials: N
authors.lastname: Shunsuke
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Funayama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Arimoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shishido
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000235:genetics / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D008822:Mice, Transgenic; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Apoptosis; Macrophage; MafB; Plaque stability