A study of role of phospholipase A2 receptor in pathogenosis ofcardiovascular diseases and development of new drug for cardiovascular diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390158
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: University of Yamanashi
• Principal Investigator: KUGIYAMA Kiyotaka 山梨大学, 医学工学総合研究部, 教授 (00225129)
• Co-Investigator(Kenkyū-buntansha): KAWABATA Kenichi 山梨大学, 医学部附属病院, 講師 (30345706) ; OBATA Jun-ei 山梨大学, 医学部附属病院, 講師 (60362076) ; SAITO Yukio 山梨大学, 大学院・医学工学総合研究部, 助教 (50377511) ; WATANABE Kazuhiro 山梨大学, 医学部附属病院, 医員 (50535549) ; WATANABE Yohsuke 山梨大学, 医学部附属病院, 医員 (90535551) ; MISHINA Hideto 山梨大学, 医学部附属病院, 医員 (70568021) ; YANO Toshiaki 山梨大学, 医学部附属病院, 医員 (60456449)
• Project Period (FY): 2010 – 2012
• Keywords: 心筋梗塞 / 炎症 / 心血管病 / ノックアウトマウス / 分泌型ホスホリパーゼA2受容体

Research Abstract

This study was aimed to examine a possible role of secretory PLA2receptor in the pathogenesis of cardiovascular diseases and to develop a new drug forprevention from cardiovascular diseases. As a result, (1) PLA2R－/－mice had a higherprevalence of cardiac rupture after MI compared with the PLA2R+/+mice. PLA2R－/－mice hada low content of collagen and a reduction in the number of myofibroblasts and theexpression of profibrogenic molecules in the infarct region. (2) The ovalbumin(OVA)-induced airway inflammation, characterized by an increased number of eosinophilsand neutrophils in BAL fluid and inflammatory histological changes in airway, was strongerin PLA2R－/－mice than in PLA2R+/+mice.

Research Products

• [Journal Article] Chronicdepletion of glutathione exacerbatesventricular remodelling and dysfunctionin the pressure-overloaded heart (2013)
  • Author(s): Watanabe Y, Watanabe K, Kobayashi T,Saito Y, Fujioka D, Nakamura T, Obata JE,Kawabata K, Mishina H, Kugiyama K
  • Journal Title: Cardiovasc Res Volume: Vol. 97, No. 2 Pages: 282-92
  • Peer Reviewed
• [Journal Article] Disruption of group IVAcytosolic phospholipase A(2) attenuatesmyocardial ischemia-reperfusion injurypartly through inhibition ofTNF-α-mediated pathway (2012)
  • Author(s): Saito Y, Watanabe K, Fujioka D, NakamuraT, Obata JE, Kawabata K, Watanabe Y,Mishina H, Tamaru S, Kita Y, Shimizu T,Kugiyama K
  • Journal Title: Am J PhysiolHeart Circ Physiol Volume: Vol.302,No.10 Pages: H2018-30
  • Peer Reviewed
• [Journal Article] Group X secretory PLA2 in neutrophilsplays a pathogenic role in abdominalaortic aneurysms in mice (2012)
  • Author(s): Watanabe K, Fujioka D, Saito Y, NakamuraT, Obata JE, Kawabata K, Watanabe Y,Mishina H, Tamaru S, Hanasaki K, KugiyamaK
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: Vol.302, No. 1 Pages: H95-104
  • Peer Reviewed
• [Journal Article] Group V secretoryphospholipase A2 plays a pathogenic rolein myocardial ischaemia-reperfusioninjury (2011)
  • Author(s): Yano T, Fujioka D, Saito Y, KobayashiT, Nakamura T, Obata JE, Kawabata K,Watanabe K, Watanabe Y, Mishina H, TamaruS, Kugiyama K
  • Journal Title: Cardiovasc Res Volume: Vol. 90,No. 2 Pages: 335-43
  • Peer Reviewed
• [Presentation] Chronic Depletion of GlutathioneExacerbates Ventricular Remodeling andDysfunction in Pressure Overloaded Heartin Mice Lacking the Glutamate-CysteineLigase Modifier Subunit (2012)
  • Author(s): Yosuke Watanabe,Kazuhiro Watanabe, Tsuyoshi Kobayashi,Yukio Saito, Daisuke Fujioka, TakamitsuNakamura, Jun-ei Obata, Kenichi Kawabata,Hideto Mishina, and Kiyotaka Kugiyama
  • Organizer: 米国心臓病学会
  • Place of Presentation: ロサンゼルス、アメリカ
  • Year and Date: 20121100
• [Presentation] Group X Secretory Phospholipase A2 inNeutrophils Plays a Pathogenic Role inAbdominal Aortic Aneurysms in Mice (2011)
  • Author(s): Kazuhiro Watanabe, Daisuke Fujioka, YukioSaito, Takamitsu Nakamura, Jun-ei Obata,Kenichi Kawabata, Yosuke Watanabe, HidetoMishina, Shun Tamaru, and KiyotakaKugiyama
  • Organizer: 米国心臓病学会
  • Place of Presentation: オーランド、アメリカ
  • Year and Date: 20111100
• [Presentation] Group V Secretory Phospholipase A2Plays a Role in Myocardial IschemiaReperfusion Injury Through CytosolicPhospholipase A2 (2010)
  • Author(s): Toshiaki Yano, KenichiKawabata, Yukio Saito, Kazuhiro Watanabe,Yosuke Watanabe, Hideto Mishina, ShunTamaru, Junei Obata, and Kiyotaka Kugiyama
  • Organizer: 米国心臓病学会
  • Place of Presentation: シカゴ、アメリカ
  • Year and Date: 20101100