Gender differences in the mechanism of hypertensive organ damage in the heart

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590839
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kurume University
• Principal Investigator: KAI Hisashi Kurume University, 医学部, 准教授 (60281531)
• Co-Investigator(Kenkyū-buntansha): KUDO Hiroshihiroshi 久留米大学, 医学部, 助教 (10373135) ; IKEDA Ayami 久留米大学, 医学部, 助教 (80412500)
• Co-Investigator(Renkei-kenkyūsha): MORI Takahiro 久留米大学, 医学部, 助教 ; TAKAYAMA Narimasa 久留米大学, 医学部, 助教 ; YASUOKA Suguru 久留米大学, 医学部, 助教 ; KAJIMOTO Hidemi 久留米大学, 循環器病研究所, 助教 ; KOGA Mitsuhisa 久留米大学, 循環器病研究所, 研究員 ; HIROOKA Yoshitaka 九州大学, 医学部, 講師
• Project Period (FY): 2007 – 2008
• Keywords: 心不全 / 高血圧 / 性差医学 / 炎症 / 分子生物学

Research Abstract

圧負荷に対する心リモデリング(代償性心筋肥大、反応性心筋線維化)およびに拡張能障害に正常メスWKY とオスWKY に差はみられなかった。しかしながら、閉経後モデルである卵巣摘出を行った卵巣摘出WKYでは、血圧負荷の程度が正常メスおよびオスと変わらず代償性心筋肥大と同等であったにもかかわらず、反応性心筋線維化およびそれに伴う左室拡張能障害は有意に増悪した。圧負荷により心筋内血管および血管周囲組織に惹起される炎症反応が卵巣摘出メスWKY において助長されることが、その原因と考えられた。さらに卵巣摘出WKY において酸化ストレスが持続的に亢進していることが炎症反応が助長される機序として考えられた。また、estradiol 補充により卵巣摘出の影響が抑制されたことから、卵巣摘出WKY と正常メスWKY の圧負荷に対する反応の違いは、estradiol 欠乏によることが示唆された。血圧変動により高血圧性心リモデリングが増悪し収縮機能障害が進展するが卵巣摘出によりこの変化が助長される。現在、レーザーマイクロダイセクション法により、各モデルの心筋細胞、血管細胞、浸潤細胞における遺伝子発現の経時的変化、細胞間クロストークにつき、コンピュータ解析中である。

Research Products

• [Journal Article] Long-term treatment with valsartan improved cyclic variation of the myocardial integral backscatter signal and diastolic dysfunction in hypertensive patients -The echorcardiographic assessment- (2008)
  • Author(s): Mizuta Y, Kai H, Mizoguchi M, Osada K, Tahara N, Nakaura H, Kuwahara F, Imaizumi T
  • Journal Title: Hypertens Res 31(10) Pages: 1843-1849
• [Journal Article] Vitamin C reversed the malfunction of peripheral blood-derived mononuclear cells in chronic smokers through the anti-oxidative property (2008)
  • Author(s): Takeshita Y, Katuski Y, Katsuda Y, Kai H, Saito Y, Arima K, Sasaki K-I, Imaizumi T
  • Journal Title: Circ J 72(4) Pages: 654-659
• [Journal Article] Usefulness of high concentration calcium chloride solution for correction of activated partial thromboplastin time (APTT) in patients with high hematocrit value. (2008)
  • Author(s): Kanahara M, Kai H, Okamura T, Wada T, Suda K, Imaizumi T, Sagawa K
  • Journal Title: Thromb Res 121(6) Pages: 781-785
• [Journal Article] Mutant MCP-1 Therapy Inhibits Tumor Angiogenesis and Growth of Malignant Melanoma in Mice. (2008)
  • Author(s): Koga M, Kai H, Egami K, Murohara T, Ikeda A, Yasuoka S, Egashira K, Matsuishi T, Kai M, Kataoka Y, Kuwano M, Imaizumi T
  • Journal Title: Biochem Biophys Res Comm 365(2) Pages: 279-284
• [Journal Article] 治療抵抗性高LDL コレステロール血症に対するアプローチ (2008)
  • Author(s): 甲斐久史
  • Journal Title: Medical Practice 25(3) Pages: 536
• [Journal Article] 高用量ストロングスタチン服用を必要とする難治性高LDL コレステロール血症に対するエゼチミブ隔日投与併用療法の有用性 (2008)
  • Author(s): 甲斐久史, 今泉 勉
  • Journal Title: Progress in Medicine 28(1) Pages: 159-163
• [Journal Article] The Prevalence of inflammation in carotid atherosclerosis. First prospective analysis with fluorodeoxyglucose positron emission tomography and carotid ultrasonography (2007)
  • Author(s): Tahara N, Kai H, Nakaura H, Ishibashi M, Hayabuchi N, Imaizumi T
  • Journal Title: Eur Heart J 28(18) Pages: 2243-2248
• [Journal Article] Reply to a letter to the Editor. Simvastatin attenuates plaque inflammation. -Evaluation by fluorodeoxyglucose positron emission tomography. (2007)
  • Author(s): Kai H, Tahara N, Ishibashi M, Imaizumi T
  • Journal Title: J Am Coll Cardiol 49(19) Pages: 1991-1992
• [Journal Article] Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is strongly associated with the metabolic syndrome. (2007)
  • Author(s): Tahara N, Kai H, Yamagishi S, Mizoguchi M, Nakaura H, Ishibashi M, Kaida H, Baba K, Hayabuchi N, Imaizumi T
  • Journal Title: J Am Coll Cardiol 49(14) Pages: 1533-1539
• [Journal Article] Inhibition of progression and stabilization of plaques by postnatal interferon-γ function blocking in ApoE-KO mice. (2007)
  • Author(s): Koga M, Kai H, Yasukawa H, Yamamoto T, Kato S, Kusaba K, Kai M, Egashira K, Kataoka T, Imaizumi T
  • Journal Title: Circ Res 101(4) Pages: 348-356
• [Journal Article] Inhibition of intrinsic interferon-γ function prevents neointima formation after vascular injury. (2007)
  • Author(s): Kusaba K, Kai H, Koga M, Takayama N, Ikeda A, Yasukawa H, Seki Y, Egashira K, Imaizumi T
  • Journal Title: Hypertension 49(4) Pages: 909-915
• [Journal Article] Estrogen withdrawal prolonged vascular inflammation and oxidative stress and aggravated diastolic function in pressureoverloaded female rats.
  • Author(s): Mori T, Kai H, Koga M, Ikeda A, Fukui D, Yasukawa H, Kai M, Imaizumi T
  • Journal Title: 投稿中
• [Journal Article] Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II-mediated chronic inflammation
  • Author(s): Kudo H, Kai H, Koga M, Takayama N, Mori T, Ikeda A, Yasuoka S, Kajimoto H, Mifune H, Kato S, Hirooka H, Imaizumi T
  • Journal Title: 投稿中
• [Presentation] レーザーマイクロダイセクション法を用いた心筋構成細胞の選択的遺伝子発現解析法の開発 (2008)
  • Author(s): 池田理望, 甲斐久史, 安岡逸, 梶本英美, 今泉勉
  • Organizer: 第30回日本高血圧学会
  • Place of Presentation: 札幌
  • Year and Date: 20081009-11
• [Presentation] Valsartan improved myocardial fibrosis and diastolic dysfunction in hypertensive patients, preferentially in patients with severe fibrosis. (2008)
  • Author(s): Mizuta Y, Kai H, (他4 名2 番目)
  • Organizer: 62^<nd> High Blood Pressure Research Conference 2008 and Scientific Sessions of the Council for High Blood Pressure Research
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20080917-20
• [Presentation] Simvastatin attenuates large blood pressure variability-induced aggravation of cardiac hypertrophy, but not myocardial fibrosis, by inhibiting Ras-ERK and Rho A pathways in hypertensive rats. .New cardioproteictive effects of statins- (2008)
  • Author(s): Takayama N, Kai H, (他8 名2 番目)
  • Organizer: 62^<nd> High Blood Pressure Research Conference 2008 and Scientific Sessions of the Council for High Blood Pressure Research
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20080917-20
• [Presentation] Role of Asymmetric Dimethylarginine in endothelial dysfunction in renal failure mice. (2008)
  • Author(s): Kajimoto H, Kai H, (他3 名2 番目)
  • Organizer: 62^<nd> High Blood Pressure Research Conference 2008 and Scientific Sessions of the Council for High Blood Pressure Research
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20080917-20
• [Presentation] Blood pressure variability-induced aggravation of end-organ damages is another achievable target of hypertension treatment .Effects of angiotensin receptor blocker in animal model- (2007)
  • Author(s): Kudo H, Kai H (他9 名2 番目)
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Orlando, USA
  • Year and Date: 20071104-07
• [Presentation] Interferon-gamma-mediated CD40/CD40 ligand pathway activation mediates atherosclerotic plaque progression and destabilization in apoE-knockout mice. (2007)
  • Author(s): Ikeda A, Kai H (他2 名2 番目)
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Orlando, USA
  • Year and Date: 20071104-07
• [Presentation] Blood pressure variability-induced aggravation of end-organ damages is another achievable target of hypertension treatment. Effects of angiotensin receptor blocker in animal model- (2007)
  • Author(s): Kudo H, Kai H (他6 名2 番目)
  • Organizer: European Society of Cardiology Congress 2007
  • Place of Presentation: Wien, Austria
  • Year and Date: 20070901-05
• [Presentation] Estrogen withdrawal aggravates myocardial fibrosis and diastolic dysfunction in pressure-overloaded female rats by enhancing perivascular inflammation and oxidative stress. (2007)
  • Author(s): Mori T, Kai H (他6 名2 番目)
  • Organizer: European Society of Cardiology Congress 2007
  • Place of Presentation: Wien, Austria
  • Year and Date: 20070901-05
• [Presentation] Mesenchymal stem cell-based prostacyclin synthase gene therapy for monocrotaline-induced pulmonary hypertension. (2007)
  • Author(s): Takemiya K, Kai H (他11 名2 番目)
  • Organizer: European Society of Cardiology Congress 2007
  • Place of Presentation: Wien, Austria
  • Year and Date: 20070901-05
• [Presentation] Valsartan attenuated myocardial fibrosis and diastolic dysfunction of hypertensive hypertrophied hearts in humans. Assessment using integrated backscatter analysis. (2007)
  • Author(s): Mizuta Y, Kai H (他2 名2 番目)
  • Organizer: European Society of Cardiology Congress 2007
  • Place of Presentation: Wien, Austria
  • Year and Date: 20070901-05