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2011 Fiscal Year Final Research Report

Analysis of the Crosstalk between Myocardium and Vasculature:Mechanism of Prevention of Hypertension by Intervention in Prehypertensive Stage

Research Project

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Project/Area Number 21590943
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKurume University

Principal Investigator

KAI Hisashi  久留米大学, 医学部, 准教授 (60281531)

Co-Investigator(Kenkyū-buntansha) KAJIMOTO Hidemi  久留米大学, 循環器病研究所, 助教 (50349700)
YASUOKA Suguru  久留米大学, 医学部, 助教 (10461435)
ANAGAWA Takahiro  久留米大学, 医学部, 助教 (00511833)
IKEDA Ayami  久留米大学, 医学部, 助教 (80412500)
Project Period (FY) 2009 – 2011
Keywords高血圧 / 心筋細胞 / 血管平滑筋 / 遺伝子発現 / 細胞間クロストーク
Research Abstract

We established a selective and comprehensive gene expression pattern analysis separating the myocardium and vasculature in the heart using the laser microdissection(LMD) method. To investigate the effects of pharmacological intervention at the prehypertensive phase on the development of hypertension, an angiotensin II receptor blocker(ARB) was administered to stroke-prone spontaneously hypertensive rats(SHR-SP) of 4-7 weeks old. SHR-SP with early exposure to ARB showed significantly lower blood pressure at hypertensive stage than those without ARB treatment. Also, the incidence of stroke and the incidence of all cause death were significantly lower in SHR-SP with ARB early exposure than those without ARB. The mRNA expression patterns of the myocardium area and vascular area were being compared separately between SHR-SP with and without ARB early exposure. A rat model of a combination of hypertension and large blood pressure variability(BPV) was created by performing a sino-aortic denervation in spoitaneously hypertensive rats. In normotensive rats, increased BPV induced only limited cardiac hypertrophy and fibrosis. In contrast, large BPV exaggerated cardiac hypertrophy and fibrosis, leading to LV systolic dysfunction in SHR. It was reveled that chronic inflammation of the intramyocardial arterioles elicited the large BPV-induced aggravation of cardiac remodeling. The gene expression profile changes induced specifically by a combination of hypertension and large BPV were being investigated separately in the myocardium area and vascular area.

  • Research Products

    (36 results)

All 2012 2011 2010 2009 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (23 results)

  • [Journal Article] Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure : new effect of asymmetric dimethylarginine2012

    • Author(s)
      Kajimoto H, Kai H, Yasuoka S, Anegawa T, (他5名2番目)
    • Journal Title

      Kidney Int

      Volume: 81 Pages: 762-768

    • Peer Reviewed
  • [Journal Article] High-sensitive troponin T is associated with atrial fibrillation in a general population2012

    • Author(s)
      Anegawa T, Kai H, (他11名2番目)
    • Journal Title

      Int J Cardiol

      Volume: 156 Pages: 98-100

    • Peer Reviewed
  • [Journal Article] Stent-anchored coil embolotherapy. Novel treatment procedure for huge pulmonary arterio-venous malformation in hereditary hemorrhagic telangiectasia2012

    • Author(s)
      Koiwaya H, Kai H, Anegawa T, (他14名2番目)
    • Journal Title

      Int J Cardiol

      Volume: 157(1) Pages: 122-124

    • Peer Reviewed
  • [Journal Article] Losartan/hydrochlorothiazide combination versus high dose losartan in patients with morning hypertension-A prospective, randomized, open-labeled, parallel-group, multicenter trial2012

    • Author(s)
      Ueda T, Kai H, Imaizumi T
    • Journal Title

      Hypertens Res online publication

    • Peer Reviewed
  • [Journal Article] Low diastolic blood pressure may not be an independent risk for cardiovascular death in revascularized coronary artery disease patients2011

    • Author(s)
      Kai H, (他6名1番目)
    • Journal Title

      J Hypertens

      Volume: 29(10) Pages: 1889-1896

    • Peer Reviewed
  • [Journal Article] Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats-A possible mechanism of diastolic dysfunction in postmenopausal women-2011

    • Author(s)
      Mori T, Kai H, Kajimoto H, Ikeda A, Yasuoka S, Anegawa T, (他5名2番目)
    • Journal Title

      Hypertens Res

      Volume: 34 Pages: 496-502

    • Peer Reviewed
  • [Journal Article] Reduction and activation of circulating dendritic cells in patients with decompensated heart failure2011

    • Author(s)
      Sugi Y, Kai H, (他9名3番目)
    • Journal Title

      Int J Cardiol

      Volume: 147(2) Pages: 258-264

    • Peer Reviewed
  • [Journal Article] Simvastatin prevents large blood pressure variability-induced aggravation of cardiac hypertrophy in hypertensive rats by inhibiting RhoA/Ras-ERK pathways2011

    • Author(s)
      Takayama N, Kai H, Yasuoka S, Anegawa T, Kajimoto H, (他4名2番目)
    • Journal Title

      Hypertens Res

      Volume: 34 Pages: 341-347

    • Peer Reviewed
  • [Journal Article] Autologous Transplantation of Bone Marrow Mononuclear Cells Improved Ischemic Peripheral Neuropathy in Humans2010

    • Author(s)
      Arima K, Kai H, (他9名9番目)
    • Journal Title

      J Am Coll Cardiol

      Volume: 56(3) Pages: 238-239

    • Peer Reviewed
  • [Journal Article] Inhibition of pigment epithelium-derived factor(PEDF) augments vascular endothelial growth factor(VEGF)-induced recovery of limb perfusion after ischemia in Klitho mouse2010

    • Author(s)
      Arima K, Kai H, (他8名8番目)
    • Journal Title

      Lett Drug Des Discov

      Volume: 7(7) Pages: 541-545

    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension in rats2010

    • Author(s)
      Takemiya K, Kai H, (他4名2番目)
    • Journal Title

      Basic Res Cardiol

      Volume: 105 Pages: 409-417

    • Peer Reviewed
  • [Journal Article] Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II system-mediated chronic inflammation2009

    • Author(s)
      Kudo H, Kai H, Kajimoto H, Ikeda A, Yasuoka S, Anegawa T, (他7名2番目)
    • Journal Title

      Hypertension

      Volume: 54 Pages: 832-838

    • Peer Reviewed
  • [Journal Article] Selective gene expression analysis of muscular and vascular components in hearts using laser microdissection method

    • Author(s)
      Ikeda A, Kai H, Kajimoto H, Yasuoka S, (他2名2番目)
    • Journal Title

      Int J Vasc Med

      Volume: (in press)

    • Peer Reviewed
  • [Presentation] Inhibition of CaMKII-and ERK-mediated eNOS phosphorylation impairs endothelial function in renal failure rats : New effect of asymmetric dimethylarginine2011

    • Author(s)
      Kajimoto H, Kai H, Aoki Y, Yasuoka S, Anegawa T, Aoki H, Imaizumi T
    • Organizer
      American Heart Association Scientific Meeting 2011
    • Place of Presentation
      Orlando, USA
    • Year and Date
      20111112-16
  • [Presentation] p21-activated kinase-mineralocorticoid receptor pathway aggravates cardiac inflammation and remodeling in hypertensive rats with large blood pressure variability2011

    • Author(s)
      Yasuoka S, Kai H, Kajimoto H, Kudo H, Takayama N, Anegawa T, Aoki Y, Iwamoto Y, Fukuda K, Imaizumi T
    • Organizer
      American Heart Association Scientific Meeting 2011
    • Place of Presentation
      Orlando, USA
    • Year and Date
      20111112-16
  • [Presentation] パネルディスカッション「血圧変動の新たな視点」Beyond Blood Pressure Variability Lowering Effect-ARBの新たな可能性-2011

    • Author(s)
      甲斐久史、今泉勉
    • Organizer
      第34回日本高血圧学会総会
    • Place of Presentation
      宇都宮
    • Year and Date
      20111020-22
  • [Presentation] on behalf of CREDO-Kyoto Investigators. Low diastolic blood pressure is not an independent risk for cardiovascular death in revascularized coronary artery disease patients ? A subanalysis CREDO-Kyoto study ?2011

    • Author(s)
      Kai H, Ueno T, Kimura T, Adachi H, Furukawa Y, Kita T, Imaizumi T
    • Organizer
      European Society of Cardiology Congress 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      20110827-31
  • [Presentation] JCS-APCS Joint Symposium."Diastolic dysfunction" fibroinflammatory changes and diastolic dysfunction in hypertensive hypertrophied hearts-From the bench to the bedside-2011

    • Author(s)
      Kai H, Imaizumi T
    • Organizer
      第75回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      20110803-04
  • [Presentation] Dimethylarginine dimethylaminohydrolase protect vascular damage in CKD mice2010

    • Author(s)
      Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Imaizumi T
    • Organizer
      American Heart Association Scientific Meeting 2010
    • Place of Presentation
      Chicago, USA
    • Year and Date
      20101113-17
  • [Presentation] エプレレノンは自然発症高血圧ラットにおいて血圧変動の増大により引き起こされる高血圧性心リモデリングを抑制する2010

    • Author(s)
      安岡逸、甲斐久史、工藤博司、高山成政、梶本英美、姉川敬裕、今泉勉
    • Organizer
      第33回日本高血圧学会総会
    • Place of Presentation
      福岡
    • Year and Date
      20101015-17
  • [Presentation] Eplerenone Prevented the Large Blood Pressure Variability-Induced Aggravation of Hypertensive Cardiac Remodeling and Left Ventricular Dysfunction in Spontaneously Hypertensive Rats2010

    • Author(s)
      安岡逸、甲斐久史、工藤博司、高山成政、梶本英美、姉川敬裕、今泉勉
    • Organizer
      第14回日本心不全学会
    • Place of Presentation
      東京
    • Year and Date
      20101007-09
  • [Presentation] Eplerenone prevented the large blood pressure variability-induced aggravation of cardiac remodeling by inhibiting of perivascular inflammation in spontaneously hypertensive rats2010

    • Author(s)
      Yasuoka S, Kai H, Kajimoto H, Kudo H, Takayama N, Anegawa T, Imaizumi T
    • Organizer
      European Society of Cardiology Congress 2010
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      20100828-0901
  • [Presentation] 血圧変動による高血圧性臓器障害の増悪-アンジオテンシンIIの重要性-2010

    • Author(s)
      工藤博司、甲斐久史、高山成政、安岡逸、今泉勉
    • Organizer
      第52回日本老年医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      20100624-26
  • [Presentation] Korea-Japan Joint Symposium : Clinic, Home, Ambulatory and Central BP in Hypertensive Management : Impact of large blood pressure variability on hypertensive cardiac remodeling-Lesson from animal models-2010

    • Author(s)
      Kai H
    • Organizer
      19th Korean Society of Hypertension Annual Congress
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      20100515-16
  • [Presentation] Effects of diastolic blood pressure levels on long-term prognosis in patients with stable coronary artery disease-Subanalysis of CREDO-Kyoto Registry-2010

    • Author(s)
      Kai H, Ueno T, Adachi H, Kimura T, Furukawa Y, Kita T, Imaizumi T
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      20100305-07
  • [Presentation] Smad-Msx-2 Pathway Plays an Initial Role in Vascular Calcification in CKD Mice2010

    • Author(s)
      Kajimoto H, Kai H, Yasuoka S, Anegawa T, Imaizumi T
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      20100305-07
  • [Presentation] Eplerenone prevented the large blood pressure variability-induced aggravation of perivascular inflammation and cardiac remodeling in spontaneously hypertensive rats2010

    • Author(s)
      Yasuoka S, Kai H, Kajimoto H, Kudo H, Takayama N, Anegawa T, Imaizumi T
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      20100305-07
  • [Presentation] Asymmetric dimethylarginine plays a triggering role in vasculo-renal interaction in CKD mice2009

    • Author(s)
      Kajimoto H, Kai H, Yasuoka S, Anegawa T, Aoki H, Imaizumi T
    • Organizer
      American Heart Association Scientific Meeting 2009
    • Place of Presentation
      Orlando, Florida
    • Year and Date
      20091115-17
  • [Presentation] Enhanced cardiac inflammation and myocardial fibrosis in ovariectomized, pressure-overloaded rats-A possible mechanism of aggravation of diastolic dysfunction in the post-menopause-2009

    • Author(s)
      Mori T, Kai H, Kajimoto H, Kudo H, Takayama N, Ikeda A, Yasuoka S, Anegawa T, Imaizumi T
    • Organizer
      American Heart Association Scientific Meeting 2009
    • Place of Presentation
      Orlando, Florida
    • Year and Date
      20091115-17
  • [Presentation] 「心筋リモデリングの分子機構」血圧変動による高血圧心リモデリング助長のメカニズム2009

    • Author(s)
      甲斐久史
    • Organizer
      第13回日本心不全学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      20091030-1101
  • [Presentation] Asymmetric Dimethylarginineが慢性腎不全における血管機能を制御している2009

    • Author(s)
      梶本英美、甲斐久史、安岡逸、青木浩樹、姉川敬裕、今泉勉
    • Organizer
      第13回日本心不全学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      20091030-1101
  • [Presentation] レーザーマイクロダイセクション法による心筋構成細胞の選択的遺伝子発現解析法2009

    • Author(s)
      安岡逸、甲斐久史、池田理望、梶本英美、姉川敬裕、今泉勉
    • Organizer
      第13回日本心不全学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      20091030-1101
  • [Presentation] 「内皮と脈管疾患」腎-血管連関-ADMAによる内皮障害-2009

    • Author(s)
      甲斐久史
    • Organizer
      第50回日本脈管学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20091029-31
  • [Presentation] 腎不全マウスにおける血清Asymmetric Dimethylarginineの上昇が血管内皮に与える影響2009

    • Author(s)
      梶本英美、甲斐久史、安岡逸、青木浩樹、姉川敬裕、今泉勉
    • Organizer
      第32回日本高血圧学会
    • Place of Presentation
      大津
    • Year and Date
      20091001-03
  • [Presentation] 「高血圧ガイドラインと心臓病診療」虚血性心疾患2009

    • Author(s)
      甲斐久史
    • Organizer
      第57回日本心臓病学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20090918-20
  • [Presentation] 血清Asymmetric dimethylarginineの増加腎不全マウスにおける内皮機能障害を起こす2009

    • Author(s)
      梶本英美、甲斐久史、安岡逸、青木浩樹、今泉勉
    • Organizer
      第56回日本心臓病学会
    • Place of Presentation
      札幌
    • Year and Date
      20090918-20

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Published: 2013-07-31  

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