Role of N-acetyl-glucosamine Metabolism in the Regulation of Macrophage Function and Atherosclerosis

• Project/Area Number: 24591117
• 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: Kyushu University
• Principal Investigator: KITAMOTO Shiro 九州大学, 医学(系)研究科(研究院), 講師 (00380436)
• Research Collaborator: BOISVERT William A. ; SUNAGAWA Kenji ; ICHIKI Toshihiro
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 動脈硬化 / マクロファージ / シグナル伝達 / 生体分子 / 糖鎖 / マイクロファージ

Outline of Final Research Achievements

O-linked N-acetyl-glucosamine (O-GlcNAc) modification was suggested to have anti-inflammatory effects of reducing M1 phenotype activation via inhibition of NF-κB transcriptional activity in cultured macrophages (Mφ), whereas augmentation of O-GlcNAc modification had no significant effects on atherosclerotic lesions of apoE deficient mice fed with Western diet. Because this apoE deficient mouse model shows hyperlipidemia and hyperglycemia and the anti-inflammatory effects of O-GlcNAc modification were blunted in high-glucose condition in cultured macrophages, O-GlcNAc modification is suggested to complexly regulate macrophage functions and mediate both anti-inflammatory and pro-inflammatory effects in the pathogenesis of atherosclerosis.

Research Products

• [Journal Article] Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice. (2014)
  • Author(s): Hashimoto T, Ichiki T, Watanabe A, Hurt-Camejo E, Michaëlsson E, Ikeda J, Inoue E, Matsuura H, Tokunou T, Kitamoto S, Sunagawa K.
  • Journal Title: Vascul Pharmacol Volume: In press Issue: 2-3 Pages: 49-55
  • DOI: 10.1016/j.vph.2014.03.006
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption. (2014)
  • Author(s): Watanabe A, Ichiki T, Sankoda C, Takahara Y, Ikeda J, Inoue E, Tokunou T, Kitamoto S, Sunagawa K.
  • Journal Title: Clin Sci Volume: 126 Issue: 9 Pages: 671-678
  • DOI: 10.1042/cs20130435
  • Peer Reviewed / Open Access
• [Journal Article] Deletion of phd2 in myeloid lineage attenuates hypertensive cardiovascular remodeling. (2013)
  • Author(s): Ikeda J, Ichiki T, Matsuura H, Inoue E, Kishimoto J, Watanabe A, Sankoda C, Kitamoto S, Tokunou T, Takeda K, Fong GH, Sunagawa K.
  • Journal Title: J Am Heart Assoc. Volume: 2 Issue: 3
  • DOI: 10.1161/jaha.113.000178
  • Peer Reviewed
• [Journal Article] Chitinase inhibition promotes atherosclerosis in hyperlipidemic mice. (2013)
  • Author(s): Kitamoto S, Egashira K, Ichiki T, Han X, McCurdy S, Sakuda S, Sunagawa K, Boisvert WA.
  • Journal Title: Am J Pathol. Volume: 183 Issue: 1 Pages: 313-325
  • DOI: 10.1016/j.ajpath.2013.04.003
  • Peer Reviewed
• [Journal Article] Chitinase Inhibition Promotes Atherosclerosis in Hyperlipidemic Mice (2013)
  • Author(s): Shiro Kitamoto, Kensuke Egashira, Toshihiro Ichiki, Xinbing Han, Sara McCurdy, Shohei Sakuda, Kenji Sunagawa, William A Boisvert
  • Journal Title: Am J Pathol. Volume: in press
  • Peer Reviewed
• [Presentation] Chitinase Inhibitor, Allosamidin, Accelerates Atherosclerotic Lesions in Hyperlipidemic Mice by Influencing M1/M2 Polarization and Cholesterol Metabolism in Macrophages
  • Author(s): Shiro Kitamoto, Kensuke Egashira, Toshihiro Ichiki, Xinbing Han, Shohei Sakuda, Kenji Sunagawa, William A Boisvert
  • Organizer: American Heart Association 2012 Scientific Sessions
  • Place of Presentation: Los angels, LA, USA