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教室紹介

診療・研究内容

(6)虚血性心臓病

我々の研究グループでは、虚血性心臓病の病態解明や新しい治療法の開発を目指して、研究を行っています。現在特に力を入れているのが、体外衝撃波治療です。非常に弱い出力の衝撃波(尿路結石破砕治療に用いる出力の10分の1)を体外から虚血心筋に当てると、心筋血流が改善することを大型動物(ブタ)および重症狭心症症例で報告しています。
[臨床研究 (1)虚血グループの項目をご参照下さい]

大型動物(ブタ)を用いた検討

慢性心筋虚血モデル・急性心筋梗塞モデル・虚血再灌流モデル・冠攣縮モデルを作成し、体外衝撃波治療や各種薬剤の効果を検討しています。

In vivo studyのために、我々は昨年度、3号館12階の動物実験施設に、大型動物用の心血管造影室を立ち上げました。ここでは、実際にブタに急性心筋梗塞を作成した後に、衝撃波治療を行い、慢性期に心機能の回復を評価しています。

小動物(ラット、マウス)を用いた検討
  1. 組織虚血に対する内因性のエリスロポエチン-エリスロポエチン受容体系の役割
    私達は、心筋虚血モデル・心肥大モデル・肺高血圧症・下肢虚血モデルを用いた検討により、組織が虚血にさらされた際に内因性のエリスロポエチン-エリスロポエチン受容体系が、血管内皮前駆細胞の動員などを介して、組織保護的に働くことを明らかにしました。

  2. 生活習慣病による心機能への影響
    心血管疾患の主要な危険因子である糖尿病や高血圧症が心機能に与える影響、および、Rho-kinase阻害薬をはじめとした各種薬物による治療効果を検討しています。
培養細胞を用いた検討
  1. 体外衝撃波治療の作用機序解明
    虚血性心臓病に対する体外衝撃波治療の詳細な作用機序を明らかにするため、培養血管内皮細胞・平滑筋細胞・心筋細胞などを用いて検討を行っています。

  2. 圧負荷が動脈硬化進展に与える影響
    拍動している動脈壁の平滑筋は、圧負荷が常に変動する環境におかれています。培養血管平滑筋細胞に与える圧負荷を変動させることにより、血管の拍動が血管平滑筋の遊走能や動脈硬化進展に与える影響を検討しています。
主な研究業績 (2000年以降)
2017年
  1. Ogata T, Ito K, Shindo T, Hatanaka K, Eguchi K, Kurosawa R, Kagaya Y, Monma Y, Ichijo S, Taki H, Kanai H, Shimokawa H. Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates contractile dysfunction of pressure-overloaded heart in mice.PLOS ONE. 12:e0185555,2017.PDF
  2. Ito K, Shindo T, Shimokawa H. Low-energy extracorporeal shock wave therapy. In: Higashi Y, Murohara T (eds.). Therapeutic Angiogenesis. pp. 177-190. Springer Nature, Singapore, 2017.PDF
  3. Ohyama K, Matsumoto Y, Amamizu H, Uzuka H, Nishimiya K, Morosawa S, Hirano M, Watabe H, Funaki Y, Miyata S, Takahashi J, Ito K, Shimokawa H. Association of coronary perivascular adipose tissue inflammation and DES-induced coronary hyperconstricting responses in pigs -FDG PET imaging study- Arterioscler Thromb Vasc Biol. 37:1757-1764,2017.PDF
  4. Godo S, Shimokawa H. Recent highlights of ATVB: Endothelial functions. Arterioscler Thromb Vasc Biol. 37:e108-e114,2017.PDF
  5. Shimokawa H, Kikuchi N, Satoh K. Shrinking basic cardiovascular research in Japan -The tip of the iceberg- Circ Res. 121:331-334,2017.PDF
2016年
  1. Hatanaka K, Ito K, Shindo T, Kagaya Y, Ogata T, Eguchi K, Kurosawa R, Shimokawa H. Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: Roles of mechanotransduction. Am J Physiol. 311:C378-385,2016.PubMed
  2. Nishimiya K, Matsumoto Y, Uzuka H, Ogata T, Hirano M, Shindo T, Hasebe Y, Tsuburaya R, Shiroto T, Takahashi J, Ito K, Shimokawa H. Beneficial effects of novel bioabsorbable polymer coating on enhanced coronary vasoconstricting responses after drug-eluting stent implantation in pigs in vivo. JACC Cardiovasc Interv. 9:281-291,2016.PDF
  3. Shimokawa H, Sunamura S, Satoh K. RhoA/Rho-kinase in the cardiovascular system. Circ Res. 118:352-366,2016.PDF
  4. Shindo T, Ito K, Ogata T, Hatanaka K, Kurosawa R, Eguchi K, Kagaya Y, Hanawa K, Aizawa K, Shiroto T, Kasukabe S, Miyata S, Taki H, Hasegawa H, Kanai H, Shimokawa H. Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates left ventricular dysfunction in a mouse model of acute myocardial infarction. Arterioscler Throm Vasc Biol. 36:1293-1301,2016.PubMed
  5. Suzuki K, Satoh K, Ikeda S, Sunamura S, Otsuki T, Satoh T, Kikuchi N, Omura J, Kurosawa R, Nogi M, Numano K, Sugimura K, Aoki T, Tatebe S, Miyata S, Mukherjee R, Spinale FG, Kadomatsu K, Shimokawa H. Basigin promotes cardiac fibrosis and failure in response to chronic pressure-overload in mice. Arterioscler Thromb Vasc Biol. 36:636-646,2016.PDF
  6. Yahata K, Kanno H, Ozawa H, Yamaya S, Tateda S, Ito K, Shimokawa H, Itoi E. Low-energy extracorporeal shock wave therapy promotes VEGF expression and angiogenesis and improves locomotor and sensory functions after spinal cord injury. J Neurosurg Spine. 1:1-11,2016.PDF
2015年
  1. Nishimiya K, Matsumoto Y, Shindo T, Hanawa K, Hasebe Y, Tsuburaya R, Shiroto T, Takahashi J, Ito K, Ishibashi-Ueda H, Yasuda S, Shimokawa H. Association of adventitial vasa vasorum and inflammation with coronary hyperconstriction after drug-eluting stent implantation in pigs in vivo. Circ J. 79:1787-1798,2015.PDF
  2. Nishimiya K, Matsumoto Y, Uzuka H, Oyama K, Tanaka A, Taruya A, Ogata T, Hirano M, Shindo T, Hanawa K, Hasebe Y, Hao K, Tsuburaya R, Takahashi J, Miyata S, Ito K, Akasaka T, Shimokawa H. Accuracy of optical frequency domain imaging for evaluation of coronary adventitial vasa vasorum formation after stent implantation in pigs and humans -A validation study- Circ J. 79:1323-1331,2015.PDF
  3. Shimokawa H, Satoh K. 2015 ATVB Plenary lecture: Translational research on Rho-kinase in cardiovascular medicine. Arterioscler Thromb Vasc Biol. 35:1756-1769,2015.PDF
  4. Shimokawa H, Satoh K. Light and dark of reactive oxygen species for vascular function. J Cardiovasc Pharmacol. 65:412-418,2015.PubMed
  5. Tsutsui M, Tanimoto A, Tamura M, Mukae H, Yanagihara N, Shimokawa H, Otsuji Y. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice. J Pharmacol Sci. 127:42-52,2015.PDF
2014年
  1. Abe Y, Ito K, Hao K, Shindo T, Ogata T, Kagaya Y, Kurosawa R, Nishimiya K, Satoh K, Miyata S, Kawakami K, Shimokawa H. Extracorporeal low-energy shock-wave therapy exerts anti-inflammatory effects in a rat model of acute myocardial infarction. Circ J. 78:2915-2925,2014.PDF
  2. Enkhjargal B, Godo S, Sawada A, Suvd N, Saito H, Noda K, Satoh K, Shimokawa H. Endothelial AMPK regulates blood pressure and coronary flow responses through hyperpolarization mechanism in mice. Arterioscler Thromb Vasc Biol. 34:1505-1513,2014.PDF
  3. Hanawa K, Ito K, Aizawa K, Shindo T, Nishimiya K, Hasebe Y, Tsuburaya R Hasegawa H, Yasuda S, Kanai H, Shimokawa H. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia. PLoS One. 2014;9(8):e104863.PDF
  4. Noda K, Nakajima S, Godo S, Saito H, Ikeda S, Shimizu T, Enkhjargal B, Fukumoto Y, Tsukita S, Yamada T, Katagiri H, Shimokawa H. Rho-kinase inhibition ameliorates metabolic disorders through activation of AMPK pathway in mice. PLoS One. 2014;9(11):e110446.PDF
  5. Sakata Y, Shimokawa H. Ischemic heart disease. In: Wakabayashi I, Groschner K (eds), Interdisciplinary Concepts of Cardiovascular Health. pp.1-17. Springer, Wien, Austria. 2014.
  6. Satoh K, Godo S, Saito H, Enkhjargal S, Shimokawa H. Dual roles of vascular-derived reactive oxygen species -With a special reference to hydrogen peroxide and cyclophilin A- J Mol Cell Cardiol. 73:50-56,2014.PDF
  7. Satoh K, Shimokawa H. High-sensitivity C-reactive protein: Still need for next-generation biomarkers for remote future cardiovascular events. Eur Heart J. 35:1776-1778,2014. (Editorial)PDF
  8. Shimokawa H. 2014 William Harvey Lecture. Importance of coronary vasomotion abnormalities -From bench to bedside- Eur Heart J. 35:3180-3193,2014.PDF
  9. Shimokawa H, Satoh K. Recent Highlights of ATVB: Vascular function. Arteriosclr Thromb Vasc Biol. 34:2359-2362,2014.
  10. Tsutsui M, Shimokawa H, Tanimoto A, Yanagihara N, Otsuji Y. Roles of nitric oxide synthases in arteriosclerotic vascular disease-Insights from murine genetic models- J Clin Exp Cardiol. 5: 318. doi:10.4172/2155-9880.1000318,2014.PDF
  11. Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Arakaki K, Kina-Tanada M, Kubota H, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Igarashi T, Ueno S, Matsushita M, Ishiuchi S, Masuzaki H, Ohya Y, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M. Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse. J Mol Cell Cardiol. 77:29-41,2014.PDF
2013年
  1. Ito D, Ito O, Mori N, Cao P, Suda C, Yoshikazu Muroya Y, Hao K, Shimokawa H, Kohzuki M. Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure. Clin Exp Pharmacol Physiol. 40:617-625,2013.PDF
  2. Takahashi K, Matsumoto Y, Do.e Z, Kanazawa M, Satoh K, Shimizu T, Sato A, Fukumoto Y, Shimokawa H. Combination therapy with atorvastatin and amlodipine suppresses angiotensin II-induced aortic aneurysm formation. PLoS One 2013;8(8):e72558.PDF
  3. Yasuda S, Shimokawa H. The Pathogenesis of Vasospastic Angina. In: Kaski JC, Eslick GD, Bairey Merz CN (eds.), Chest Pain with Normal Coronary Arteries, pp.91-99. Springer-Verlag, London, UK, 2013.
2012年
  1. Benkhoff S, Loot AE, Pierson I, Sturza A, Kohlstedt K, Fleming I, Shimokawa H, Grisk O, Brandes RP, Schroder K. Leptin potentiates endothelium-dependent relaxation by inducing endothelial expression of neuronal NO synthase. Arteriscler, Thromb, Vasc Biol. 32:1605-1612,2012.PDF
  2. Hayashi D, Kawakami K, Ito K, Ishii K, Tanno H, Imai Y, Kanno E, Maruyama R, Shimokawa H, Tachi M. Low-energy extracorporeal shock wave therapy enhances skin wound healing in diabetic mice: a critical role of endothelial nitric oxide synthase. Wound Repair Regen. 20:887-895,2012.PDF
  3. Kromhout D, Yasuda S, Geleijnse JM, Shimokawa H. Fish oil and omega-3 fatty acids in cardiovascular disease: do they really work? Eur Heart J. 33:436-443,2012.PDF
  4. Nakajima S, Ohashi J, Sawada A, Noda K, Fukumoto Y, Shimokawa H. Essential role of bone marrow for microvascular endothelial and metabolic functions in mice. Circ Res. 111:87-96,2012.PDF
  5. Noda K, Hosoya M, Nakajima S, Ohashi J, Fukumoto Y, Shimokawa H. Anti-atherogenic effects of the combination therapy with olmesartan and azelnidipine in diabetic apolipoprotein e-deficient mice. Tohoku J Exp Med. 228:305-315,2012.PDF
  6. Ohashi J, Sawada A, Nakajima S, Noda K, Takaki A, Shimokawa H. Mechanisms for enhanced endothelium-derived hyperpolarizing factor-mediatedresponses in microvessels in mice. Circ J. 76:1768-1779,2012.PDF
  7. Tsuburaya R, Yasuda S, Shiroto T, Ito Y, Gao JY, Aizawa K, Kikuchi Y, Ito K, Takahashi J, Ishibashi-Ueda H, Shimokawa H. Long-term treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo: possible involvement of Rho-kinase pathway. Eur Heart J. 33:791-799,2012.PDF
  8. Satoh K, Fukumoto Y, Nakano M, Kagaya Y, Shimokawa H. Emergence of the erythropoietin/erythropoietin receptor system as a novel cardiovascular therapeutic target. J Cardiovasc Pharmacol. 58:570-574,2012.PubMed
2011年
  1. Gao JY, Yasuda S, Tsuburaya R, Ito Y, Shiroto T, Hao K, Aizawa K, Kikuchi Y, Ito K, Shimokawa H. Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo -Involvement of Rho-kinase pathway inhibition- Circ J. 75:1843-1851,2011.PDF
  2. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy for ischemic cardiovascular disorders. Am J Cardiovasc Drugs. 11:295-302,2011.PubMed
  3. Kikuchi Y, Yasuda S, Aizawa K, Tsuburaya R, Ito Y, Takeda M, Nakayama M, Ito K, Takahashi J, Shimokawa H. Enhanced Rho-kinase activity in circulating neutrophils of patients with vasospastic angina: a possible biomarker for diagnosis and disease activity assessment. J Am Coll Cardiol. 58:1231-1237,2011.PDF
  4. Satoh K, Berk BC, Shimokawa H. Vascular-derived reactive oxygen species for homeostasis and diseases. Nitric Oxide. 25:211-215,2011. (Review)PubMed
  5. Satoh K, Fukumoto Y, Shimokawa H. Rho-kinase: Important new therapeutic target in cardiovascular diseases. Am J Physiol. 301:287-296,2011.PDF
  6. Serizawa F, Ito K, Matsubara M, Sato A, Shimokawa H, Satomi S. Extracorporeal Shock Wave Therapy Induces Therapeutic Lymphangiogenesis in a Rat Model of Secondary Lymphoedema. Eur J Vasc Endovasc Surg. 42:254-260,2011.PDF
  7. Tsuburaya R, Yasuda S, Ito Y, Shiroto T, Gao JY, Ito K, Shimokawa H. Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs. J Mol Cell Cardiol. 51:329-336,2011.PDF
2010年
  1. Ito K, Kagaya Y, Shimokawa H. Thyroid hormone and chronically unloaded hearts. Vascul Pharmacol. 52:138-141,2010.PubMed
  2. Ito Y, Ito K, Shiroto T, Tsuburaya R, Yi GJ, Takeda M, Fukumoto Y, Yasuda S, Shimokawa H. Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo. Coron Artery Dis. 21:304-311,2010.PubMed
  3. Kikuchi Y, Ito K, Ito Y, Shiroto T, Tsuburaya R, Aizawa K, Hao K, Fukumoto Y, Takahashi J, Takeda M, Nakayama M, Yasuda S, Kuriyama S, Tsuji I, Shimokawa H. Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris. Circ J. 74:589-591,2010.PDF
  4. Matsumoto Y, Adams V, Jacob S, Mangner N, Schuler G, Linke A. Regular exercise training prevents aortic valve disease in low-density lipoprotein-receptor-deficient mice. Circulation. 121:759-767,2010.PubMed
  5. Nakano M, Fukumoto Y, Satoh K, Ito Y, Kagaya Y, Ishii N, Sugamura K, Shimokawa H. OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization. Cardiovasc Res. 1;88(3):539-46,2010 Dec.PubMed
  6. Shimokawa H, Ito K. Extracorporeal cardiac shock wave therapy for ischemic heart disease. In: Achim M. Loske (ed.), New Trends in Shock Wave Applications to Medicine and Biotechnology, Research Signpost, India, 211-224,2010.
2009年
  1. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. Tohoku J Exp Med. 219:1-9,2009.PDF
  2. Lenk K, Schur R, Linke A, Erbs S, Matsumoto Y, Adams V, Schuler G. Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model. Eur J Heart Fail. 11:342-348,2009.PDF
  3. Masumiya H, Asaumi Y, Nishi M, Minamisawa S, Adachi-Akahane S, Yoshida M, Kangawa K, Ito K, Kagaya Y, Yanagisawa T, Yamazaki T, Ma J, Takeshima H. Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes. Channels (Austin). 3:6-11,2009.PDF
  4. Matsumoto Y, Adams V, Walther C, Kleinecke C, Brugger P, Linke A, Walther T, Mohr FW, Schuler G. Reduced number and function of endothelial progenitor cells in patients with aortic valve stenosis: a novel concept for valvular endothelial cell repair. Eur Heart J. 30:346-355,2009.PDF
  5. Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Takahashi J, Ito K, Ishibashi-Ueda H, Shimokawa H. Role of Rho-kinase in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in pigs in vivo. J Am Coll Cardiol. 54:2321-2329,2009.PDF
2008年
  1. Fukumoto Y, Yasuda S, Ito A, Shimokawa H. Prognostic effects of benidipine in patients with vasospastic angina: comparison with diltiazem and amlodipine. J Cardiovasc Pharmacol. 51:253-257,2008.PubMed
  2. Ito K, Shimokawa H. Extracorporeal cardiac shock wave therapy for angina pectoris. Nippon Rinsho. 66:2019-2026,2008.PubMed
  3. Kokusho Y, Komaru T, Takeda S, Takahashi K, Koshida R, Shirato K, Shimokawa H. Hydrogen peroxide derived from beating heart mediates coronary microvascular dilation during tachycardia. Arterioscler Thromb Vasc Biol. 27:1057-1063,2008.PubMed
  4. Oi K, Fukumoto Y, Ito K, Uwatoku T, Abe K, Hizume T, Shimokawa H. Extracorporeal shock wave therapy ameliorates hind-limb ischemia in rabbits. Tohoku J Exp Med. 214:151-158,2008.PubMed
  5. Shimokawa H, Ito K, Fukumoto Y, Yasuda S. Extracorporeal cardiac shock wave therapy for ischemic heart disease. Shock Waves. 17:449-455,2008.
  6. Tada T, Nawata J, Wang H, Onoue N, Zhulanqiqige D, Ito K, Sugimura K, Fukumoto Y, Shimokawa H. Enhanced pulsatile pressure accelerates vascular smooth muscle migration: implications for atherogenesis of hypertension. Cardiovasc Res. 17:449-455,2008.PubMed
2007年
  1. Asaumi Y, Kagaya Y, Takeda M, Yamaguchi N, Tada H, Ito K, Ohta J, Shiroto T, Shirato K, Minegishi N, Shimokawa H. Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice. Circulation. 115:2022-2032,2007.PubMed
  2. Minatoya Y, Ito K, Kagaya Y, Asaumi Y, Takeda M, Nakayama M, Takahashi J, Iguchi A, Shirato K, Shimokawa H. Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats. Acta Physiol (Oxf). 189:221-231,2007.PubMed
  3. Nakano M, Satoh K, Fukumoto Y, Ito Y, Kagaya Y, Ishii N, Sugamura K, Shimokawa H. Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice. Circ Res. 100:662-669,2007.PubMed
  4. Uwatoku T, Ito K, Abe K, Oi K, Hizume T, Sunagawa K, Shimokawa H. Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs. Coron Artery Dis. 18:397-404,2007.PubMed
  5. Yada T, Shimokawa H, Hiramatsu O, Shinozaki Y, Mori H, Goto M, Ogasawara Y, Kajiya F. Important role of endogenous hydrogen peroxide in pacing-induced metabolic coronary vasodilation in dogs in vivo. J Am Coll Cardiol. 50:1272-1278,2007.PDF
  6. Yada T, Shimokawa H, Morikawa K, Takaki A, Shinozaki Y, Mori H, Goto M,Ogasawara Y, Kajiya F. Role of Cu,Zn-SOD in the synthesis of endogenous hydrogen peroxide during reactive hyperemia in mouse mesentetric microcirculation in vivo. Am J Physiol. 294:441-448,2007.PDF
2006年
  1. Fukumoto Y, Ito A, Uwatoku T, Matoba T, Kishi T, Tanaka H, Takeshita A, Sunagawa K, Shimokawa H. Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coron Artery Dis. 17:63-70,2006.PubMed
  2. Hizume T, Morikawa K, Takaki A, Abe K, Sunagawa K, Amano M, Kaibuchi K, Kubo C, Shimokawa H. Sustained elevation of serum cortisol level causes sensitization of coronary vasoconstricting responses in pigs in vivo: a possible link between stress and coronary vasospasm. Circ Res. 99:767-775,2006.PubMed
  3. Satoh K, Kagaya Y, Nakano M, Ito Y, Ohta J, Tada H, Karibe A, Minegishi N, Suzuki N, Yamamoto M, Ono M, Watanabe J, Shirato K, Ishii N, Sugamura K, Shimokawa H. Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. Circulation. 113:1442-1450,2006.PubMed
  4. Tada H, Kagaya Y, Takeda M, Ohta J, Asaumi Y, Satoh K, Ito K, Karibe A, Shirato K, Minegishi N, Shimokawa H. Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion.Cardiovasc Res. 71:466-477,2006.PubMed
2005年
  1. Eto Y, Shimokawa H, Fukumoto Y, Matsumoto Y, Morishige K, Kunihiro I, Kandabashi T, Takeshita A. Combination therapy with cerivastatin and nifedipine improves endothelial dysfunction after balloon injury in porcine coronary arteries. J Cardiovasc Pharmacol. 46:1-6,2005.PubMed
  2. Ito K, Hirooka Y, Hori N, Kimura Y, Sagara Y, Shimokawa H, Takeshita A, Sunagawa K. Inhibition of rho-kinase in the nucleus tractus solitarius enhances glutamate sensitivity in rats. Hypertension. 46:360-365,2005.PubMed
  3. Ito K, Hirooka Y, Kimura Y, Shimokawa H, Takeshita A. Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats. Clin Exp Hypertens. 27:269-277,2005.PubMed
  4. Kimura Y, Hirooka Y, Sagara Y, Ito K, Kishi T, Shimokawa H, Takeshita A, Sunagawa K. Overexpression of inducible nitric oxide synthase in rostral ventrolateral medulla causes hypertension and sympathoexcitation via an increase in oxidative stress. Circ Res. 96:252-260,2005.PubMed
  5. Kishi T, Hirooka Y, Masumoto A, Ito K, Kimura Y, Inokuchi K, Tagawa T, Shimokawa H, Takeshita A, Sunagawa K. Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. Circulation. 111:2741-2747,2005.PubMed
  6. Namiuchi S, Kagaya Y, Ohta J, Shiba N, Sugi M, Oikawa M, Kunii H, Yamao H, Komatsu N, Yui M, Tada H, Sakuma M, Watanabe J, Ichihara T, Shirato K. High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention. J Am Coll Cardiol. 45:1406-1412,2005.PubMed
  7. Sakai K, Hirooka Y, Shigematsu H, Kishi T, Ito K, Shimokawa H, Takeshita A, Sunagawa K. Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction. Am J Physiol. 289:H2159-2166,2005.PubMed
2004年
  1. Ito K, Hirooka Y, Kishi T, Kimura Y, Kaibuchi K, Shimokawa H, Takeshita A. Rho/Rho-kinase pathway in the brainstem contributes to hypertension caused by chronic nitric oxide synthase inhibition. Hypertension. 43:156-162,2004.PubMed
  2. Ito K, Hirooka Y, Sagara Y, Kimura Y, Kaibuchi K, Shimokawa H, Takeshita A, Sunagawa K. Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats. Hypertension. 44:478-483,2004.PubMed
  3. Kishi T, Hirooka Y, Kimura Y, Ito K, Shimokawa H, Takeshita A. Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation. 109:2357-2362,2004.PubMed
  4. Matsumoto Y, Uwatoku T, Oi K, Abe K, Hattori T, Morishige K, Eto Y, Fukumoto Y, Nakamura K, Shibata Y, Matsuda T, Takeshita A, Shimokawa H. Long-term inhibition of Rho-kinase suppresses neointimal formation after stent implantation in porcine coronary arteries: involvement of multiple mechanisms. Arterioscler Thromb Vasc Biol. 24:181-186,2004.PubMed
  5. Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, Matsumoto Y, Kajihara N, Eto M, Matsuda T, Yasui H, Takeshita A, Sunagawa K. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation. 110:3055-3061,2004.PubMed
  6. Oi K, Shimokawa H, Hiroki J, Uwatoku T, Abe K, Matsumoto Y, Nakajima Y, Nakajima K, Takeichi S, Takeshita A. Remnant lipoproteins from patients with sudden cardiac death enhance coronary vasospastic activity through upregulation of Rho-kinase. Arterioscler Thromb Vasc Biol. 24:918-922,2004.PubMed
2003年
  1. Hirooka Y, Sakai K, Kishi T, Ito K, Shimokawa H, Takeshita A. Enhanced depressor response to endothelial nitric oxide synthase gene transfer into the nucleus tractus solitarii of spontaneously hypertensive rats. Hypertens Res. 26:325-331,2003.PubMed
  2. Inokuchi K, Hirooka Y, Shimokawa H, Sakai K, Kishi T, Ito K, Kimura Y, Takeshita A. Role of endothelium-derived hyperpolarizing factor in human forearm circulation. Hypertension. 42:919-924,2003.PubMed
  3. Ito K, Nakayama M, Hasan F, Yan X, Schneider MD, Lorell BH. Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts. Circulation. 107:1176-1182,2003.PubMed
  4. Ito K, Hirooka Y, Sakai K, Kishi T, Kaibuchi K, Shimokawa H, Takeshita A. Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via sympathetic nervous system: possible involvement in neural mechanisms of hypertension. Circ Res. 92:1337-1343,2003.PubMed
  5. Kandabashi T, Shimokawa H, Miyata K, Kunihiro I, Eto Y, Morishige K, Matsumoto Y, Obara K, Nakayama K, Takahashi S, Takeshita A. Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm. Arterioscler Thromb Vasc Biol. 23:2209-2214,2003.PubMed
  6. Kishi T, Hirooka Y, Kimura Y, Sakai K, Ito K, Shimokawa H, Takeshita A. Overexpression of eNOS in RVLM improves impaired baroreflex control of heart rate in SHRSP. Rostral ventrolateral medulla. Stroke-prone spontaneously hypertensive rats. Hypertension. 41:255-260,2003.PubMed
  7. Morishige K, Shimokawa H, Matsumoto Y, Eto Y, Uwatoku T, Abe K, Sueishi K, Takeshita A. Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo. Cardiovasc Res. 57:572-585,2003.PubMed
  8. Shimokawa H, Eto Y, Miyata K, Morishige K, Kandabashi T, Matsushima K, Takeshita A. Propagermanium suppresses macrophage-mediated formation of coronary arteriosclerotic lesions in pigs in vivo. J Cardiovasc Pharmacol. 41:372-380,2003.PubMed
2002年
  1. Kishi T, Hirooka Y, Ito K, Sakai K, Shimokawa H, Takeshita A. Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats. Hypertension. 39:264-268,2002.PubMed
  2. Matsumoto Y, Shimokawa H, Morishige K, Eto Y, Takeshita A. Reduction in neointimal formation with a stent coated with multiple layers of releasable heparin in porcine coronary arteries. J Cardiovasc Pharmacol. 39:513-522,2002.PubMed
2001年
  1. Ito K, Yan X, Feng X, Manning WJ, Dillmann WH, Lorell BH. Transgenic expression of sarcoplasmic reticulum Ca(2+) atpase modifies the transition from hypertrophy to early heart failure. Circ Res. 89:422-429,2001.PubMed
  2. Morishige K, Shimokawa H, Eto Y, Hoshijima M, Kaibuchi K, Takeshita A. In vivo gene transfer of dominant-negative rho-kinase induces regression of coronary arteriosclerosis in pigs. Ann N Y Acad Sci. 947:407-411,2001.PubMed
  3. Morishige K, Shimokawa H, Eto Y, Kandabashi T, Miyata K, Matsumoto Y, Hoshijima M, Kaibuchi K, Takeshita A. Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. Arterioscler Thromb Vasc Biol. 21:548-554,2001.PubMed
  4. Sato S, Ikegaki I, Asano T, Shimokawa H. Antiischemic properties of fasudil in experimental models of vasospastic angina. Jpn J Pharmacol. 87:34-40,2001.PubMed
  5. Shimokawa H, Morishige K, Miyata K, Kandabashi T, Eto Y, Ikegaki I, Asano T, Kaibuchi K, Takeshita A. Long-term inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo. Cardiovasc Res. 51:169-177,2001.PubMed
2000年
  1. Eto Y, Shimokawa H, Hiroki J, Morishige K, Kandabashi T, Matsumoto Y, Amano M, Hoshijima M, Kaibuchi K, Takeshita A. Gene transfer of dominant negative Rho kinase suppresses neointimal formation after balloon injury in pigs. Am J Physiol. 278:H1744-1750,2000.PubMed
  2. Ito K, Yan X, Tajima M, Su Z, Barry WH, Lorell BH. Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts. Circ Res. 87:588-595,2000.PubMed
  3. Kandabashi T, Shimokawa H, Miyata K, Kunihiro I, Kawano Y, Fukata Y, Higo T, Egashira K, Takahashi S, Kaibuchi K, Takeshita A. Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta. Circulation. 101:1319-1323,2000.PubMed
  4. Kuga T, Shimokawa H, Hirakawa Y, Kadokami Y, Arai Y, Fukumoto Y, Kuwata K, Kozai T, Egashira K, Takeshita A. Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm. J Cardiovasc Pharmacol. 35:822-828,2000.PubMed
  5. Miyata K, Shimokawa H, Higo T, Yamawaki T, Katsumata N, Kandabashi T, Tanaka E, Takamura Y, Yogo K, Egashira K, Takeshita A. Sarpogrelate, a selective 5-HT2A serotonergic receptor antagonist, inhibits serotonin-induced coronary artery spasm in a porcine model. J Cardiovasc Pharmacol. 35:294-301,2000.PubMed
  6. Miyata K, Shimokawa H, Kandabashi T, Higo T, Morishige K, Eto Y, Egashira K, Kaibuchi K, Takeshita A. Rho-kinase is involved in macrophage-mediated formation of coronary vascular lesions in pigs in vivo. Arterioscler Thromb Vasc Biol. 20:2351-2358,2000.PubMed
  7. Morishige K, Shimokawa H, Yamawaki T, Miyata K, Eto Y, Kandabashi T, Yogo K, Higo T, Egashira K, Ueno H, Takeshita A. Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo. J Am Coll Cardiol. 35:1040-1047,2000.PubMed

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