The impact of macrophage transcription factor MafB on rupture of abdominal aortic aneurysm

• Project/Area Number: 24591033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Yamagata University
• Principal Investigator: WATANABE Tetsu 山形大学, 医学部, 講師 (40359568)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 腹部大動脈瘤 / マクロファージ / MafB / 転写因子MafB / ニコチン / 喫煙 / PET/CT

Outline of Final Research Achievements

Transcription factor MafB is expressed only in monocytes and macrophages among hematopoietic cells, which plays a role in the terminal differentiation of macrophages. MafB knockout mice die immediately after birth due to developmental anomalies of neurons in the respiratory centre. We generated transgenic mice that express dominant negative (DN) MafB capable of suppressing endogenous MafB transcription activity only in macrophages. The abdominal aortic aneurysm (AAA) model was developed by 1000 ng/kg/min of angiotensin II infusion in apolipoprotein E-deficient (ApoE KO) mice and ApoE KO/DN MafB mice. There was no difference in development of AAA between ApoE KO mice and ApoE KO/DN MafB mice. We investigate impact of MafB on rupture of AAA.

Research Products

• [Journal Article] A novel mouse model of aortic valve stenosis induced by direct wire injury. (2014)
  • Author(s): Honda S, Miyamoto T, Watanabe T, Narumi T, Kadowaki S, Honda Y, Otaki Y, Hasegawa H, Netsu S, Funayama A, Ishino M, Nishiyama S, Takahashi H, Arimoto T, Shishido T, Miyashita T, Kubota I.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 34 Issue: 2 Pages: 270-278
  • DOI: 10.1161/atvbaha.113.302610
  • Peer Reviewed
• [Journal Article] Midkine exacerbates pressure overload-induced cardiac remodeling. (2014)
  • Author(s): Netsu S, Shishido T, Kitahara T, Honda Y, Funayama A, Narumi T, Kadowaki S, Takahashi H, Miyamoto T, Arimoto T, Nishiyama S, Watanabe T, Woo CH, Takeishi Y, Kubota I.
  • Journal Title: Biochem Biophys Res Commun. Volume: 443 Issue: 1 Pages: 205-210
  • DOI: 10.1016/j.bbrc.2013.11.083
  • Peer Reviewed / Open Access
• [Journal Article] Atrial endothelial impairment through Toll-like receptor 4 signaling causes atrial thrombogenesis. (2014)
  • Author(s): Katoh S, Honda S, Watanabe T, Suzuki S, Ishino M, Kitahara T, Funayama A, Netsu S, Sasaki T, Shishido T, Miyamoto T, Sadahiro M, Kubota I.
  • Journal Title: Heart Vessels. Volume: 29 Issue: 2 Pages: 263-272
  • DOI: 10.1007/s00380-013-0369-3
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase α exacerbates cardiac injury after ischemia/reperfusion. (2014)
  • Author(s): Sasaki T, Shishido T, Kadowaki S, Kitahara T, Suzuki S, Katoh S, Funayama A, Netsu S, Watanabe T, Goto K, Takeishi Y, Kubota I.
  • Journal Title: Heart Vessels. Volume: 29 Issue: 1 Pages: 110-118
  • DOI: 10.1007/s00380-013-0366-6
  • Peer Reviewed
• [Journal Article] Cardiac nuclear High Mobility Group Box 1 prevents the development of cardiac hypertrophy and heart failure. (2013)
  • Author(s): Funayama A, Shishido T, Netsu S, Narumi T, Kadowaki S, Takahashi H, Miyamoto T, Watanabe T, Woo CH, Abe JI, Kuwahara K, Nakao K, Takeishi Y, Kubota I.
  • Journal Title: Cardiovasc Res. Volume: 99 Issue: 4 Pages: 657-64
  • DOI: 10.1093/cvr/cvt128
  • Peer Reviewed
• [Journal Article] Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction. (2013)
  • Author(s): Suzuki S et al.
  • Journal Title: PLOS ONE Volume: 8 Issue: 1 Pages: e53133-e53133
  • DOI: 10.1371/journal.pone.0053133
  • Peer Reviewed
• [Presentation] Plasma thioredoxin-1 level is associated with renal tubular damage and predicts poor prognosis in patients with chronic heart failure. (2013)
  • Author(s): 8) Otaki Y, Watanabe T, Takahashi H, Tamura H, Nishiyama S, Arimoto T, Miyashita T, Shishido T, Miyamoto T, Kubota I
  • Organizer: ESC CONGRESS
  • Place of Presentation: Amsterdam RAI convention center （Amsterdam, Netherlands）
• [Presentation] The role of macrophage transcriptional factor MafB in atherosclerotic plaque stability. (2013)
  • Author(s): 11) Hasegawa H, Kato S, Watanabe T, Takahashi H, Arimoto T, Shishido T, Miyashita T, Miyamoto T, Shibata Y, Kubota I
  • Organizer: ESC CONGRESS
  • Place of Presentation: Amsterdam RAI convention center （Amsterdam, Netherlands）
• [Presentation] Cardiac-specific overexpression of high-mobility group box 1 attenuates cardiomyocyte apoptosis and mitochondrial dysfunction during the pathogenesis of doxorubicin cardiomyopathy. (2013)
  • Author(s): 16) Narumi T, Shishido T, Funayama A, Yokoyama M, Kinoshita D, Kadowaki S, Honda Y, Otaki Y, Nishiyama S, Takahashi H, Arimoto T, Miyashita T, Miyamoto T, Watanabe T, Kubota I
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Dallas convention center （Dallas, TX, USA）
• [Presentation] Ubiquitin E3 ligase ITCH ameliorates reactive oxygen species-induced cardiotoxicity through interaction with thioredoxin-interacting protein. (2013)
  • Author(s): 19) Otaki Y, Takahashi H, Watanabe T, Narumi T, Kadowaki S, Honda Y, Arimoto T, Shishido T, Miyashita T, Miyamoto T, Kubota I
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Dallas convention center （Dallas, TX, USA）
• [Presentation] Inhibition of macrophage transcriptional factor MafB exacerbates atherosclerotic plaque vulnerability (2012)
  • Author(s): 長谷川寛真、渡邉哲
  • Organizer: American Heart Association Scientific meeting 2012
  • Place of Presentation: ﾛｻﾝｾﾞﾙｽｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ (ｶﾘﾌｫﾙﾆｱ､ｱﾒﾘｶ)