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

Research Project

Project/Area Number 21591140
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe 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
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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 / メタボリックシンドローム / 2型糖尿病
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.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (41 results)

All 2012 2011 2010 2009

All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (12 results)

  • [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

      Volume: 2011 Pages: 175381-175381

    • DOI

      10.4061/2011/175381

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors2011

    • 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 Issue: 2 Pages: 225-31

    • DOI

      10.1038/hr.2010.211

    • NAID

      10031163157

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ezetimibe Monotherapy Ameliorates Vascular Function in Patients with Hypercholesterolemia Through Decreasing Oxidative Stress2011

    • Author(s)
      Kurobe H
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 18 Issue: 12 Pages: 1080-1089

    • DOI

      10.5551/jat.9548

    • NAID

      130004845358

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interactions between CKD and MetS and the Development of CVD2011

    • Author(s)
      Aihara K, et al
    • Journal Title

      Cardiol Res Pract

      Volume: article ID 878065 Pages: 1-2

    • DOI

      10.4061/2011/878065

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Low-dose (1mg/day) "Pitavastatin" on Left Ventricular Diastolic Function and Albuminuria in Patients with Hyperlipidemia2011

    • Author(s)
      赤池雅史
    • Journal Title

      Am J Cardiol

      Volume: 107 Issue: 11 Pages: 1644-1649

    • DOI

      10.1016/j.amjcard.2011.01.054

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function2011

    • Author(s)
      Ikeda Y, Tajima S, Yoshida S, Yamano N, Kihira Y, Ishizawa K, Aihara K, Tomita S, Tsuchiya K and Tamaki T
    • Journal Title

      Atherosclerosis

      Volume: 215 Issue: 2 Pages: 339-347

    • DOI

      10.1016/j.atherosclerosis.2011.01.009

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bosentan improves systemic sclerosis-related peripheral circulation insufficiency.2011

    • Author(s)
      Yagi S, et al.
    • Journal Title

      Int J Cardiol.

      Volume: 147 Pages: 472-475

    • Related Report
      2010 Annual Research Report
    • 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, et al.
    • Journal Title

      Hypertens Res.

      Volume: 34 Pages: 225-231

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of peroxisome proliferator-activated receptor α in megakaryocytes reduces platelet-derived growth factor-BB in platelets.2011

    • Author(s)
      Hashizume S, et al.
    • Journal Title

      J Atheroscler Thromb.

      Volume: 18 Pages: 138-147

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High plasma aldosterone concentration is a novel risk factor of cognitive impairment in patients with hypertension.2011

    • Author(s)
      Yagi S, et al.
    • Journal Title

      Hypertens Res.

      Volume: 34 Pages: 74-78

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice2010

    • 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 Issue: 3 Pages: 430-6

    • DOI

      10.1161/hypertensionaha.110.152207

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/ db mice2010

    • 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 Issue: 2 Pages: 513-9

    • DOI

      10.1210/en.2009-0661

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transforming growth factor-β1 as a common target molecule for development of cardiovascular diseases, renal insufficiency and metabolic syndrome.2010

    • Author(s)
      Aihara K, et al.
    • Journal Title

      Cardiol Res Pract.

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bosentan ameliorated exercise-induced pulmonary arterial hypertension complicated with systemic sclerosis.2010

    • Author(s)
      Yagi S, et al.
    • Journal Title

      Intern Med.

      Volume: 49 Pages: 2309-2012

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparin cofactor II attenuates vascular remodeling in humans and mice2010

    • Author(s)
      Aihara K
    • Journal Title

      Circ J.

      Volume: 74 Pages: 1518-1523

    • Related Report
      2010 Annual Research Report
    • 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, et al.
    • Journal Title

      Hypertension.

      Volume: 56 Pages: 430-436

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dehydroepiandrosterone sulfate is inversely associated with sex-dependent diverse carotid atherosclerosis regardless of endothelial function.2010

    • Author(s)
      Yoshida S, et al.
    • Journal Title

      Atherosclerosis.

      Volume: 212 Pages: 310-315

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Androgen receptor counteracts Doxorubicin-induced cardiotoxicity in male mice.2010

    • Author(s)
      Ikeda Y, et al.
    • Journal Title

      Mol Endocrinol.

      Volume: 24 Pages: 1338-1348

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Congenital ventricular aneurysm as an unexpected complication of monomorphic premature ventricular contractions.2010

    • Author(s)
      Yagi S, et al.
    • Journal Title

      Intern Med.

      Volume: 49 Pages: 907-912

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury.2010

    • Author(s)
      Yagi S, et al.
    • Journal Title

      Hypertension.

      Volume: 55 Pages: 918-923

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] eNOS-independent Protective Action of Statin Against Angiotensin II-induced Atrial Remodeling via Reduced Oxidant Injury.2010

    • Author(s)
      Yagi, S
    • Journal Title

      Hypertension 55

      Pages: 918-923

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ezetimide ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.2010

    • Author(s)
      Yagi, S
    • Journal Title

      J Atheroscler Thromb 17

      Pages: 173-180

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Thrombin Action Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice.2010

    • Author(s)
      Mihara, M
    • Journal Title

      Endocrinology 151

      Pages: 513-519

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of hypoxia-inducible factor lalpha in T cells as a negative regulator in development of vascular remodeling.2010

    • Author(s)
      Kurobe, H
    • Journal Title

      Arterioscler Thromb Vase Biol. 30

      Pages: 210-217

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparin cofactor II as a novel vascular protective factor against atherosclerosis2009

    • Author(s)
      Aihara K, Azuma H, Akaike M, Sata M, Matsumoto T
    • Journal Title

      J Atheroscler Thromb

      Volume: 16 Pages: 523-31

    • NAID

      10026143124

    • URL

      http://dx.doi.org/10.5551/jat.1552

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Androgen-androgen receptor system protects against angiotensin II-induced vascular remodeling.2009

    • Author(s)
      Ikeda, Y
    • Journal Title

      Endocrinology 150

      Pages: 2857-2864

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decrease in plasma brain natriuretic peptide level in the early phase after the start of carvediolo therapy is a novel predictor of long-term outcome in patients with chronic heart failure.2009

    • Author(s)
      Fujimura, M
    • Journal Title

      Acta Cardiol 64

      Pages: 589-595

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparin cofactor II as a novel vascular protective factor against atherosclerosis.2009

    • Author(s)
      Aihara, K
    • Journal Title

      J Atheroscler Thromb 16

      Pages: 523-531

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparin cofactor II is an independent protective factor against peripheral arterial disease in elderly subjects with cardiovascular risk factors.2009

    • Author(s)
      Aihara, K
    • Journal Title

      J Atheroscler Thromb 16

      Pages: 127-134

    • Related Report
      2009 Annual Research Report
    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] ヘパリンコファククー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
    • Related Report
      2011 Annual Research Report
  • [Presentation] Heparin cofactor II, a serine protease inhibitor, is a novel regulating factor for glucose metabolism and albuminuria2012

    • 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
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 心血管ストレスに対するアンドロゲン受容体系の役割2010

    • Author(s)
      粟飯原賢一
    • Organizer
      第1回テストステロン研究会
    • Place of Presentation
      時事通信ホール(東京都)
    • Year and Date
      2010-11-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] A role of androgen receptor in ischemia-induced tissue damage and angiogenesis in male2010

    • Author(s)
      吉田守美子, 他
    • Organizer
      第42回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      長良川国際会議場(岐阜市)
    • Year and Date
      2010-07-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] A role of androgen receptor in ischemia-induced tissue damage and angiogenesis in male2010

    • Author(s)
      粟飯原賢一, 他
    • Organizer
      日本内科学会第102回四国地方会
    • Place of Presentation
      徳島県立郷土文化会館(徳島市)
    • Year and Date
      2010-05-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] アンチエイジング検診とFMD2010

    • Author(s)
      粟飯原賢一, 他
    • Organizer
      血管不全研究会 第8回学術集会
    • Place of Presentation
      日本青年館ホテル(東京都)
    • Year and Date
      2010-04-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Heparin cofactor II is a novel anticardiac remodeling factor against angiotensin II excess2010

    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] Influence of lipid profile on endothelial function in subjects with cardiovascular risk factors2009

    • Author(s)
      粟飯原賢一
    • Organizer
      第41回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      海峡メッセ下関(山口県)
    • Year and Date
      2009-07-17
    • Related Report
      2009 Annual Research Report
  • [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
      前橋商工会議所(群馬県)
    • Year and Date
      2009-04-24
    • Related Report
      2009 Annual Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [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
    • Related Report
      2011 Final Research Report 2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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