Role of microglia in the development of cardiovascular diseases

• Project/Area Number: 25670391
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University
• Principal Investigator: ICHIKI Toshihiro 九州大学, 医学(系)研究科(研究院), 研究員 (80311843)
• Co-Investigator(Renkei-kenkyūsha): SUNAGAWA Kenji 九州大学, 大学院医学研究院, 教授 (50163043) ; KITAMOTO Shiro 九州大学, 大学院医学研究院, 講師 (00380436) ; TOKUNOU Tomotake 九州大学, 大学院医学研究院, 助教 (50567378)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 低酸素応答系 / マイクログリア / 心肥大 / 圧負荷 / 室傍核 / PHD

Outline of Final Research Achievements

Microglia is considered brain macrophage and is involved in immune response in the brain. Although macrophages play an important role in the development of cardiovascular diseases, contribution of microglia is not clear. We sought to determine whether the hypoxia response system in microglia plays any roles in the development of pressure overload-induced cardiac hypertrophy.
We generated mice with macrophage-specific deletion of prolyl hydroxylase domain protein (PHD) 2 that induces degradation of hypoxia-inducible factor. Pressure overload by constriction of transverse aorta induced slightly less cardiac hypertrophy in PHD2-deficient mice. However, activation of microglia in the paraventricular nucleus, one of the nuclei that regulate sympathetic nerve activity, was not difference between PHD2-deficient and control mice. These results suggest that the hypoxia response system in microglia plays little role in the development of pressure overload-induced cardiac hypertrophy.

Research Products

• [Journal Article] Novel roles of hypoxia response system in glucose metabolism and obesity (2014)
  • Author(s): Ichiki T, Sunagawa K
  • Journal Title: Trends Cardiovasc Med. Volume: 24 Issue: 5 Pages: 197-201
  • DOI: 10.1016/j.tcm.2014.03.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
  • Peer Reviewed
• [Journal Article] Prolyl Hydroxylase Domain Protein 2 Plays a Critical Role in Diet-induced Obesity and Glucose Intolerance. (2013)
  • Author(s): Matsuura H, Ichiki T, Inoue E, Nomura M, Miyazaki R, Hashimoto T, Ikeda J, Takayanagi R, Fong GH, Sunagawa K
  • Journal Title: Circulation Volume: 127 Pages: 2078-2087
  • Peer Reviewed
• [Presentation] Cross talk between the hypoxia response system and angiotensin II receptor (2015)
  • Author(s): 市來俊弘
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Deletion of Phd2 in Myeloid Lineage Attenuates Hypertensive Cardiovascular Remodeling (2013)
  • Author(s): Jiro Ikeda, Toshihiro Ichiki , Kenji Sunagawa
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
  • Place of Presentation: 大阪
• [Presentation] Myeloid-Specific Deletion of Prolyl Hydroxylase Domain Protein 2 Attenuates Hypertensive Cardiovascular Remodeling (2013)
  • Author(s): Toshihiro Ichiki, Jiro Ikeda, Kenji Sunagawa
  • Organizer: High Blood Pressure Research Scientific Sessions 2013
  • Place of Presentation: ニューオリンズ
• [Presentation] Myeloid-Specific Deletion of Prolyl Hydroxylase Domain Protein 2 Attenuates Hypertensive Cardiovascular Remodeling (2013)
  • Author(s): 市来俊弘
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: さいたま市
• [Remarks] 血管分子機能研究室
  • URL: https://www.med.kyushu-u.ac.jp/cardiol/kyoshitsu/blood/index.html