Pathophysiological roles of heparin cofactor II in cardiac remodeling and insulin resistance

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokushima
• Principal Investigator: AIHARA Ken-ichi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 講師 (70372711)
• Co-Investigator(Kenkyū-buntansha): AKAIKE Masashi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (90271080) ; IWASE Takashi 徳島大学, 病院, 助教 (10403718) ; ENDOU Itsurou 徳島大学, 病院, 講師 (10432759) ; HUJINAKA Yuichi 徳島大学, 病院, 講師 (30432751)
• Project Period (FY): 2009 – 2011
• Keywords: ヘパリンコファクターII / トロンビン / 心筋リモデリング / インスリン抵抗性

Research Abstract

We hypothesized that thrombin inactivation ameliorate cardiac remodeling and diabetes. Angiotensin II accelerated cardiac concentric remodeling and larger left atrial volume with prominent interstitial fibrosis in heparin cofactor II(HCII), an endogenous thrombin inhibitor,-deficient mice than those in wild-type mice. And these cardiac phenotypes were caused by enhancement of NAD(P) H oxidase-transforming growth factor-beta1 pathway. In addition, we found that increased thrombin activity in adipose tissue contributes to the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation.

Research Products

• [Journal Article] Transforming growth factor-β1 as a common target molecule for development of cardiovascular diseases, renal insufficiency and metabolic syndrome. (2011)
  • Author(s): Aihara K, Ikeda Y, Yagi S, Akaike M, Matsumoto T
  • Journal Title: Cardiol Res Pract Pages: 175381
  • DOI: DOI:10.4061/2011/175381
  • Peer Reviewed
• [Journal Article] Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors (2011)
  • Author(s): Ise T, Aihara K, Sumitomo-Ueda Y, Yoshida S, Ikeda Y, Yagi S, Iwase T, Yamada H, Akaike M, Sata M, Matsumoto T
  • Journal Title: Hypertens Res Volume: 34 Pages: 225-31
  • DOI: DOI:10.1038/hr.2010.211
  • Peer Reviewed
• [Journal Article] Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice (2010)
  • Author(s): Sumitomo-Ueda Y, Aihara K, Ise T, Yoshida S, Ikeda Y, Uemoto R, Yagi S, Iwase T, Ishikawa K, Hirata Y, Akaike M, Sata M, Kato S, Matsumoto T
  • Journal Title: Hypertension Volume: 56 Pages: 430-6
  • DOI: DOI:10.1161/HYPERTENSIONAHA.110.152207
  • Peer Reviewed
• [Journal Article] Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/ db mice (2010)
  • Author(s): Mihara M, Aihara K, Ikeda Y, Yoshida S, Kinouchi M, Kurahashi K, Fujinaka Y, Akaike M, Matsumoto T
  • Journal Title: Endocrinology Volume: 151 Pages: 513-9
  • DOI: DOI:10.1210/en.2009-0661
  • Peer Reviewed
• [Journal Article] Heparin cofactor II as a novel vascular protective factor against atherosclerosis (2009)
  • Author(s): Aihara K, Azuma H, Akaike M, Sata M, Matsumoto T
  • Journal Title: J Atheroscler Thromb Volume: 16 Pages: 523-31
  • URL: http://dx.doi.org/10.5551/jat.1552
  • Peer Reviewed
• [Presentation] ヘパリンコファクターIIは耐糖能制御因子である (2012)
  • Author(s): 粟飯原賢一
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2012-04-19
• [Presentation] Heparin cofactor II, a serine protease inhibitor, is a novel regulating factor for glucose metabolism and albuminuria (2012)
  • Author(s): Ken-ichi Aihara
  • Organizer: Keystone Symposia Complications of Diabetes : Mechanisms of Injury and Failure of Repair
  • Place of Presentation: Boston Park Plaza & Towers, Boston, Massachusetts, USA
  • Year and Date: 2012-03-14
• [Presentation] Heparin cofactor II is a novel anticardiac remodeling factor against angiotensin II excess (2010)
  • Author(s): Yuka Sumitomo-Ueda, Ken-ichi Aihara
  • Organizer: 17th International Society for Heart Research
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
  • Year and Date: 2010-03-14
• [Presentation] 尿中アルブミンは内臓脂肪蓄積の強力な増悪因子である (2009)
  • Author(s): 粟飯原賢一
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬県民会館、前橋商工会議所(前橋市)
  • Year and Date: 2009-04-23
• [Presentation] 内臓脂肪増大因子に関する臨床的検討 (2009)
  • Author(s): 粟飯原賢一
  • Organizer: 第106回日本内科学会総会・講演会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2009-04-11