Elucidation of C-reactive protein in atherosclerosis and myocardial infarction and translational research

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390099
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: University of Yamanashi
• Principal Investigator: FAN Jianglin University of Yamanashi, 大学院・医学工学総合研究部, 教授 (60272192)
• Co-Investigator(Kenkyū-buntansha): KOIKE Tomonari 山梨大学, 大学院・医学工学総合研究部, 助教 (40432158) ; TEZUKA Hideo 山梨大学, 総合分析実験センター, 准教授 (70155456) ; MORIMOTO Masatoshi 熊本保健科学大学, 保健科学部, 教授 (90136482) ; SHIOMI Masashi 神戸大学, 医学部附属動物実験施設, 准教授 (50226106)
• Project Period (FY): 2007 – 2009
• Keywords: 動脈硬化 / CRP / 遺伝子改変ウサギ / トランスレーショナル研究 / 冠状動脈硬化

Research Abstract

我が国の死因30%を占める心筋梗塞や脳卒中といった動脈硬化性疾患の分子病態解明は、国民の健康やQOLを向上させる上で重要な課題である。本研究では心筋梗塞の発症に最も関係している血清炎症マーカーであるC-反応性蛋白の生理機能および動脈硬化の発生における役割について新たに開発した遺伝子改変ウサギモデルにより検討を行った。C-反応性蛋白が動脈硬化の発生を直接に促進することは認められないものの、動脈硬化の進展に有用な診断指標としての意義を明らかにした。また、C-反応性蛋白はバルーン障害により誘導された血栓の形成を促進していることが認められた。

Research Products

• [Journal Article] Expression of human apoAII in transgenic rabbits leads to dyslipidemia: a new model for combined hyperlipidemia. (2009)
  • Author(s): Koike T, Kitajima S, Yu Y, Li Y, Nishijima K, Liu E, Sun H, Waqar AB, Shibata N, Inoue T, Wang Y, Zhang B, Kobayashi J, Morimoto M, Saku K, Watanabe T, Fan J.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29 Pages: 2047-2053
  • Peer Reviewed
• [Journal Article] Human C-reactive protein does not promote atherosclerosis in transgenic rabbits. (2009)
  • Author(s): Koike T, Kitajima S, Yu Y, Nishijima K, Zhang J, Ozaki Y, Morimoto M, Watanabe T, Bhakdi S, Asada Y, Chen YE, Fan J.
  • Journal Title: Circulation 120 Pages: 2088-2094
  • Peer Reviewed
• [Journal Article] Endotoxin accelerates atherosclerosis independent of complement activation. (2009)
  • Author(s): Reifenberg K, Lehr HA, Fan J, Koike T, Wiese E, Kupper I, Sagban TA, Schaefer SC, Zahringer U, Torzewski M, Lackner KJ, Bhakdi S.
  • Journal Title: Thromb Res. 123 Pages: 653-658
  • Peer Reviewed
• [Journal Article] The effects of rosiglitazone on aortic atherosclerosis of cholesterol-fed rabbits. (2008)
  • Author(s): Zhao S, Zhang C, Lin Y, Yang P, Yu Q, Chu Y, Yang P, Fan J, Liu E.
  • Journal Title: Thromb Res. 123 Pages: 281-287
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 12 accelerates the initiation of atherosclerosis and stimulates the progression of fatty streaks to fibrous plaques in transgenic rabbits. (2008)
  • Author(s): Yamada S, Wang KY, Tanimoto A, Fan J, Shimajiri S, Kitajima S, Morimoto M, Tsutsui M, Watanabe T, Yasumoto K, Sasaguri Y.
  • Journal Title: Am J Pathol. 172 Pages: 1419-1429
  • Peer Reviewed
• [Journal Article] Spontaneous atherosclerosis in aged lipoprotein lipase-deficient mice with severe hypertriglyceridemia on a normal chow diet. (2008)
  • Author(s): Zhang X, Qi R, Xian X, Yang F, Blackstein M, Deng X, Fan J, Ross C, Karasinska J, Hayden MR, Liu G.
  • Journal Title: Circ Res. 102 Pages: 250-256
  • Peer Reviewed
• [Journal Article] Unstable coronary plaques and cardiac events in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits: questions and quandaries. (2008)
  • Author(s): Shiomi M, Fan J.
  • Journal Title: Curr Opin Lipidol. 19 Pages: 631-636
  • Peer Reviewed
• [Journal Article] Expression of LPL in endothelial-intact artery results in lipid deposition and vascular cell adhesion molecule-1 upregulation in both LPL and ApoE-deficient mice. (2007)
  • Author(s): Wang J, Xian X, Huang W, Chen L, Wu L, Zhu Y, Fan J, Ross C, Hayden MR, Liu G.
  • Journal Title: Arterioscler Thromb Vasc Biol. 27 Pages: 197-203
  • Peer Reviewed
• [Journal Article] Increased expression of vascular endothelial growth factor in kidney leads to progressive impairment of glomerular functions. (2007)
  • Author(s): Liu E, Morimoto M, Kitajima S, Koike T, Yu Y, Shiiki H, Nagata M, Watanabe T, Fan J.
  • Journal Title: J Am Soc Nephrol. 18 Pages: 2094-2104
  • Peer Reviewed
• [Journal Article] Lp(a) enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits. (2007)
  • Author(s): Kitajima S, Jin Y, Koike T, Yu Y, Liu E, Shiomi M, Marcovina SM, Morimoto M, Watanabe T, Fan J.
  • Journal Title: Atherosclerosis. 193 Pages: 269-276
  • Peer Reviewed
• [Presentation] 動脈硬化の研究のための新たな遺伝子改変ウサギ・モデルの開発と応用. (2008)
  • Author(s): 範江林
  • Organizer: 第40回日本動脈硬化学会総会・学術集会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2008-07-11
• [Presentation] 動脈硬化の発生・進展におけるCRPの役割:Marker or Maker or both? (2007)
  • Author(s): 範江林
  • Organizer: 第8回ABカンファレンス
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2007-07-28
• [Book] Rabbit genomics, transgenesis, cloning and models: Springer(Rabbit Biotechnology) (2009)
  • Author(s): Houdebine L, Fan J.
  • Total Pages: 136
• [Remarks] ホームページ等
  • URL: http://www.med.yamanashi.ac.jp/clinical_basic/pathol01/
• [Patent(Industrial Property Rights)] ヒトC反応性蛋白遺伝子導入ウサギ (2009)
  • Inventor(s): 国立大学法人山梨大学、国立大学法人佐賀大学、MOREHOUSE COLLEGE
  • Industrial Property Rights Holder: 範江林, 他
  • Industrial Property Number: 特許,特願2009-141742
  • Filing Date: 2009-06-15
  • Acquisition Date: 2009-06-15