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教室紹介

診療・研究内容

(11)循環器先端医療開発学講座超音波治療の開発研究(基礎研究、臨床治験)

循環器先端医療開発寄附講座は、国民病ともいえる循環器疾患に対する先進的な診断・治療法を開発することを目的に、平成18年10月に開講しました。

主な研究テーマ

1. 虚血性心・肢疾患に対する非侵襲的体外衝撃波治療

低出力の衝撃波を血管内皮細胞に照射することにより各種の血管新生因子の産生が促進されることが基礎研究の結果明らかにされました。近年、虚血性心臓病・閉塞性動脈硬化症などの動脈硬化性疾患が増加しており、生命予後・QOLの悪化の原因となっています。薬物療法・カテーテル治療・バイパス手術が行われてきましたが、これらの治療法だけでは十分な効果が得られない、あるいは適応困難な重症例が増えてきています。虚血性心疾患に対する低出力の体外衝撃波照射は、副作用なく非侵襲的に繰り返し施行できる利点があり、新しい血管新生療法として多くの注目を集めており、現在、欧州を中心に世界約20ヵ国で行われています。また、当院でも重症狭心症例、急性心筋梗塞症例、下肢閉塞性動脈硬化症を対象に臨床試験を遂行しています。
臨床研究/虚血グループをご参照ください。

2. 虚血性心疾患に対する超音波治療

衝撃波治療の研究開発が進む中、当講座では、衝撃波と同じく音波の一種である低出力パルス波超音波が同様の効果を持つ可能性に注目しました。超音波を用いた場合、一つのプローブで診断と治療の両方が可能であること、組織を損傷する可能性が少ないこと、診断用装置がすでに世界中に普及していることなどから、その有効性が確認できれば汎用性は極めて高いものと考えられます。そして最近、私たちは、ある特定の照射条件の低出力パルス波超音波が培養血管内皮細胞において血管内皮増殖因子の産生を亢進させ、ブタ慢性心筋虚血モデルにおいては、血管新生が促進されて心筋虚血が改善し、心機能が向上することを突き止めました。さらに、マウス心筋梗塞モデルでは、超音波治療が梗塞領域を減少させ、慢性期の心室リモデリングを抑制し、その分子機序にメカノトランスダクションとその下流のシグナル伝達が寄与している可能性を報告しています。これらの基礎的検討をもとに、現在、難治性狭心症患者を対象とした超音波治療の医師主導治験を全国10施設で行っており、超音波治療がその症状を改善するかを検証しています。
臨床研究/虚血グループをご参照ください。

3. 医工連携

低侵襲性治療は、患者本位の次世代型医療に直結するものであり、そのための先端的・革新的な研究開発に向けて、医学者、工学者、および企業技術者の連携をより一層強化することが必要です。本寄付講座では、医療現場、研究現場で必要とされる医療機器や治療技術などの開発・臨床応用を目指し、東北大学大学院工学系研究科・金井浩教授、並びに東北大学大学院医工学系研究科との「医工連携」を推進しています。日本を牽引する医療機器開発、日本発で世界に発信できるコンセプトの創出を進めています。

図:ブタ慢性心筋虚血モデルにおける超音波治療の効果
ブタ慢性心筋虚血モデルにおける超音波治療の効果
臨床研究/虚血グループをご参照ください。

主な研究業績 (2004年以降)
2017年
  1. Aoki T, Sugimura K, Tatebe S, Miura M, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Konno R, Miyata S, Nochioka K, Satoh K, Shimokawa H. Comprehensive evaluation of the effectiveness and safety of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension -Long-term effects and procedure-related complications- Eur Heart J. (in press)
  2. Uzuka H, Matsumoto Y, Nishimiya K, Ohyama K, Suzuki H, Amamizu H, Morosawa S, Hirano M, Shindo T, Kikuchi Y, Hao K, Shiroto T, Ito K, Takahashi J, Fukuda K, Miyata S, Funaki Y, Ishibashi-Ueda H, Yasuda S, Shimokawa H. Renal denervation suppresses coronary hyperconstricting responses after drug-eluting stent implantation in pigs in vivo through the kidney-brain-heart axis. Arterioscler Thromb Vasc Biol. (in press)
  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. (in press)
  4. Hirano M, Yamamoto H, Fukuda K, Morosawa S, Amamizu H, Ohyama K, Uzuka H, Takayama K, Shimokawa H. Development of a novel shock wave catheter ablation system -A validation study in pigs in vivo- Europace. (in press)PDF
  5. Godo S, Shimokawa H. Recent highlights of ATVB: Endothelial functions. Arterioscler Thromb Vasc Biol. (in press)
  6. Satoh T, Satoh K, Yaoita N, Kikuchi N, Omura J, Kurosawa R, Numano K, Elias-Al-Mamun M, AbdulHai Siddique MAH, Sunamura S, Nogi M, Suzuki K, Miyata S, John Morser J, Shimokawa H. Activated TAFI promotes the development of chronic thromboembolic pulmonary hypertension - A possible novel therapeutic target - Circ Res. 120:1246-1262,2017.PDF
  7. Satoh K, Sugimura K, Shimokawa H. Rho-kinase as a therapeutic target for pulmonary hypertension. In: Fukumoto Y (ed), Diagnosis and Treatment of Pulmonary Hypertension. From Bench to Bedside, pp. 67-76. Springer Nature, Singapore, 2017.
  8. Godo S, Shimokawa H. Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis. Free Radical Biology & Medicine. 109:4-10,2017.PDF
  9. Crea F, Merz CNB, Beltrame JF, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Camici P: COVADIS Group. The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift. Eur Heart J. 38:473-477,2017.PDF
  10. Odaka Y, Takahashi J, Tsuburaya R, Nishimiya K, Hao K, Matsumoto Y, Ito K, Sakata Y, Miyata S, Manita D, Hirowatari Y, Shimokawa H. Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries. Eur Heart J. 38:489-496,2017.PDF
2016年
  1. Aoki T, Sugimura K, Nochioka K, Miura M, Tatebe S, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Miyata S, Satoh K, Shimokawa H. Effects of balloon pulmonary angioplasty on oxygenation in patients with chronic thromboembolic pulmonary hypertension - Importance of intra-pulmonary shunt - Circ J. 80:2227-2234,2016.PDF
  2. Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Merz CNB, the COVADIS Group. The who, what, why, when, how and where of vasospastic angina. Circ J. 80:289-298,2016.PDF
  3. 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
  4. Kanno H, Yahata K, 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. (in press)
  5. Komatsu M, Takahashi J, Fukuda K, Takagi Y, Shiroto T, Nakano M, Kondo M, Tsuburaya R, Hao K, Nishimiya K, Nihei T, Matsumoto Y, Ito K, Sakata Y, Miyata S, Shimokawa H. Usefulness of Testing for Coronary Artery Spasm and Programmed Ventricular Stimulation in Survivors of Out-of-Hospital Cardiac Arrest. Circ Arrhythm Electrophysiol. 9:doi:10.1161/CIRCEP.115.003798,2016.PDF
  6. Kudo S, Satoh K, Nogi M, Suzuki K, Sunamura S, Omura J, Kikuchi N, Kurosawa R, Satoh T, Minami T, Ikeda S, Shimokawa H. SmgGDS as a crucial mediator of the inhibitory effects of statins on cardiac hypertrophy and fibrosis. -Novel mechanism of the pleiotropic effects of statins- Hypertension. 67:878-889,2016.PDF
  7. Minami T, Satoh K, Nogi M, Kudo S, Miyata S, Tanaka S, Shimokawa H. Statins up-regulate SmgGDS through ß1-integrin/Akt1 pathway in endothelial cells. Cardiovasc Res. 109:151-161,2016.PDF
  8. Nishimiya K, Matsumoto Y, Uzuka H, Ohyama K, Hao K, Tsuburaya R, Shiroto T, Takahashi J, Ito K, Shimokawa H. Focal vasa vasorum formation in patients with focal coronary vasospasm -An optical frequency domain imaging study- Circ J. 80:2252-2254,2016.PDF
  9. Nishimiya K, Matsumoto Y, Takahashi J, Uzuka H, Wang H, Tsuburaya R, Hao K, Ohyama K, Odaka Y, Miyata S, Ito K, Shimokawa H. Enhanced adventitial vasa vasorum formation in patients with vasospastic angina -Assessment with optical frequency domain imaging- J Am Coll Cardiol. 67:598-600,2016.PDF
  10. Omura J, Satoh K, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Otsuki T, Kozu K, Numano K, Suzuki K, Sunamura S, Tatebe S, Aoki T, Sugimura K, Miyata S, Hoshikawa Y, Okada Y, Shimokawa H. Protective roles of endothelial AMP-activated protein kinase against hypoxia-induced pulmonary hypertension in mice. Circ Res. 119:197-209,2016.PDF
  11. Ohyama K, Matsumoto Y, Nishimiya K, Hao K, Tsuburaya R, Ota H, Amamizu H, Uzuka H, Takahashi J, Ito K, Shimokawa H. Increased coronary perivascular adipose tissue volume in patients with vasospastic angina. Circ J. 80:1653-1656,2016.PDF
  12. Saito S, Ishii T, Kamogawa Y, Watanabe R, Shirai T, Fujita Y, Shirota Y, Fujii H, Ito K, Shimokawa H, Yamaguchi T, Kawaguchi Y, Harigae H. Extracorporeal shock wave therapy for digital ulcers of systemic sclerosis: A phase 2 pilot study. Tohoku J Exp Med. 238:39-47,2016. PubMed
  13. Sato H, Ota H, Sugimura K, Aoki T, Tatebe S, Miura M, Yamamoto S, Yaoita N, Suzuki H, Satoh K, Takase K, Shimokawa H. Balloon pulmonary angioplasty improves biventricular functions and pulmonary flow in chronic thromboembolic pulmonary hypertension. Circ J. 80:1470-1477,2016.PDF
  14. Shimokawa H, Sunamura S, Satoh K. RhoA/Rho-kinase in the cardiovascular system. Circ Res. 118:352-366,2016.PDF
  15. Shimokawa H, Godo S. Diverse functions of endothelial NO synthases system: NO and EDH. J Cardiovasc Pharmacol. 67:361-366,2016.PDF
  16. 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
  17. Suzuki H, Matsumoto Y, Ota H, Sugimura K, Takahashi J, Ito K, Miyata S, Furukawa K, Arai H, Fukumoto Y, Taki Y, Shimokawa H. Hippocampal blood flow abnormality associated with depressive symptoms and cognitive impairment in patients with chronic heart failure. Circ J. 80:1773-1780,2016.PDF
  18. 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
  19. Takagi H, Hideki Ota H, Sugimura K, Otani K, Tominaga J, Aoki T, Tatebe S, Miura M, Yamamoto S, Sato H, Nobuhiro Yaoita N, Suzuki H, Shimokawa H, Takase K. Dual-energy CT to estimate clinical severity of chronic thromboembolic pulmonary hypertension: Comparison with invasive right heart catheterization. Eur J Radiol. 85:1574-1580,2016.PDF
  20. Tatebe S, Sugimura K, Aoki T, Miura M, Nochioka K, Miyamichi-Yamamoto S, Yaoita N, Suzuki H, Sato H, Satoh K, Fukumoto Y, Shimokawa H. Multiple beneficial effects of balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. Circ J. 80:980-988,2016.PDF
  21. 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
  22. Yaoita N, Satoh K, Satoh T, Sugimura K, Tatebe S, Yamamoto S, Aoki T, Miura M, Kawamura T, Horiuchi H, Fukumoto Y, Shimokawa H. Thrombin-activatable fibrinolysis inhibitor in chronic thromboembolic pulmonary hypertension. Arterioscler Throm Vasc Biol. 36:1220-1229,2016.PubMed
  23. Yaoita N, Satoh K, Shimokawa H. Novel therapeutic targets of pulmonary hypertension. (Review) Arteriosclr Thromb Vasc Biol. 2016;36:e97-e102. DOI: 10.1161/ATVBAHA.116.308263.PDF
  24. Zheng Y, Wei D, Zhu X, Chen W, Fukuda K, Shimokawa H. Transmural, interventricular, apicobasal and anteroposterior action potential duration gradients are all essential to the genesis of the concordant and realistic T wave: A whole-heart model study. J Electrocardiol. 2016;49:569-78,2016.PDF
2015年
  1. Ito K, Shimokawa H. The future of non-invasive angiogenic therapy using acoustic waves. Circ J. 79:1906-1907,2015.
  2. Ellawindy A, Satoh K, Sunamura S, Kikuchi N, Suzuki K, Minami T, Ikeda S, Tanaka S, Shimizu T, Enkhjargal B, Miyata S, Taguchi Y, Handoh T, Kobayashi K, Kobayashi K, Nakayama K, Miura M, ShimokawaH. Rho-kinase inhibition during early cardiac development causes arrhythmogenic right ventricular cardiomyopathy in mice. Arterioscler Thromb Vasc Biol. 35:2172-2184,2015PubMed
  3. Hasebe Y, Yamamoto H, Fukuda K, Nishimiya K, Hanawa K, Shindo T, Kondo M, Nakano M, Wakayama Y, Takayama K, Shimokawa H. Development of a novel shock wave catheter ablation system -The first feasibility study in pigs- PLoS One. 2015;10(1):e0116017.PDF
  4. 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
  5. 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
  6. Noda K, Godo S, Saito H, Tsutsui M, Shimokawa H. Opposing roles of nitric oxide and Rho-kinase in lipid metabolism in mice.Tohoku J Exp Med. 235:171-183,2015.PDF
  7. Ota H, Sugimura K, Miura M, Shimokawa H. 4D flow MRI visualizes drastic change of vortex flow in the main pulmonary artery after percutaneous transluminal balloon angioplasty in a patient with chronic thromboembolic pulmonary hypertension. Eur Heart J. 36:1630,2015.PDF
  8. Satoh K. Cyclophilin A in cardiovascular homeostasis and diseases. Tohoku J Exp Med. 235:1-15,2015.PDF
  9. Satoh K, Kikuchi N, Kurosawa R, Shimokawa H. PDE1C negatively regulates growth factor receptor degradation and promotes VSMC proliferation. Circ Res. 116:1098-1100,2015.PubMed
  10. 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
  11. Shimokawa H, Satoh K. Light and dark of reactive oxygen species for vascular function. J Cardiovasc Pharmacol. 65:412-418,2015.PubMed
  12. Suzuki H, Sumiyoshi A, Matsumoto Y, Duffy B, Yoshikawa T, Lythgoe M, Yanai K, Taki Y, Kawashima R, Shimokawa H. Structural abnormality of the hippocampus associated with depressive symptoms in heart failure rats. NeuroImage. 105:84-92,2015.PDF
  13. 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
  14. Zheng Y, Wei D, Zhu X, Chen W, Fukuda K, Shimokawa H. Ventricular fibrillation mechanisms and cardiac restitutions: An investigation by simulation study on whole-heart model. Comput Biol Med. 63:261-268,2015.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. Al-Mamun ME, Satoh K, Tanaka S, Shimizu T, Nergui S, Miyata S, Fukumoto Y, Shimokawa H. Combination therapy with fasudil and sildenafil ameliorates monocrotaline-induced pulmonary hypertension and survival in rats. Circ J. 78:967-976,2014.PDF
  3. Dai Z, Sugimura K, Fukumoto Y, Tatebe S, Miura Y, Nochioka K, Aoki T, Miyamichi-Yamamoto S, Yaoita N, Satoh K, Shimokawa H. Visualization of Complete Regression of Pulmonary Arterial Remodeling on Optical Coherence Tomography in a Patient With Pulmonary Arterial Hypertension. Circ J. 78:2771-2773,2014.PDF
  4. 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
  5. 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
  6. Ikeda S, Satoh K, Kikuchi N, Miyata S, Suzuki K, Omura J, Shimizu T, Kobayashi K, Kobayashi K, Fukumoto Y, Sakata Y, Shimokawa H. Crucial role of Rho-kinase in pressure-overload-induced right ventricular hypertrophy and dysfunction in mice. Arterioscler Thromb Vasc Biol. 34:1260-1271,2014.PDF
  7. Nergui S, Fukumoto Y, Do.e Z, Nakajima S, Shimizu T, Ikeda S, Elias-Al-Mamun M, Shimokawa H. Role of eNOS and collagen metabolism in right ventricular remodeling due to pulmonary hypertension. Circ J. 78:1465-1474,2014.PDF
  8. Nihei T, Takahashi J, Tsuburaya R, Ito Y, Shiroto T, Hao K, Takagi Y, Matsumoto Y, Nakayama M, Miyata S, Sakata Y, Ito K, Shimokawa H. Circadian variation of rho-kinase activity in circulating leukocytes of patients with vasospastic angina. Circ J. 78:1183-1190,2014.PDF
  9. 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
  10. Noguchi S, Yatera K, Wang KY, Oda K, Akata K, Yamasaki K, Kawanami T, Ishimoto H, Toyohira Y, Shimokawa H, Yanagihara N, Tsutsui M, Mukae H. Nitric oxide exerts protective effects against bleomycin-induced pulmonary fibrosis in mice. Respir Res. 15:92.doi:10.1186/s12931-014-0092-3.PDF
  11. Satoh K, Satoh T, Kikuchi N, Omura J, Kurosawa R, Suzuki K, Sugimura K, Aoki T, Nochioka K, Tatebe S, Yamamoto S, Miura M, Shimizu T, Ikeda S, Yaoita N, Fukumoto Y, Minami T, Miyata S, Nakamura K, Ito H, Kadomatsu K, Shimokawa H. Basigin mediates pulmonary hypertension by promoting inflammation and vascular smooth muscle cell proliferation. Circ Res. 115:738-750,2014.PDF
  12. Shimokawa H. 2014 William Harvey Lecture. Importance of coronary vasomotion abnormalities -From bench to bedside- Eur Heart J. 35:3180-3193,2014.PDF
  13. Shimokawa H, Satoh K. Recent Highlights of ATVB: Vascular function. Arteriosclr Thromb Vasc Biol. 34:2359-2362,2014.
  14. Suzuki H, Matsumoto Y, Kaneta T, Sugimura K, Takahashi J, Fukumoto Y, Takahashi S, Shimokawa H. Evidence for brain activation in patients with takotsubo cardiomyopathy. Circ J. 78:256-258,2014.PDF
  15. 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
  16. Yamaki S, Ando M, Fukumoto Y, Higuchi Y, Kaneko K, Maeda K, Shimokawa H. Histopathological examination by lung biopsy for the evaluation of operability and postoperative prognosis in patients with chronic thromboembolic pulmonary hypertension. Circ J. 78:476-482,2014.PDF
  17. Yamaya S, Ozawa H, Kanno H, Kishimoto KN, Sekiguchi A, Tateda S, Yahata K, Ito K, Shimokawa H, Itoi E. Low-energy extracorporeal shock wave therapy promotes VEGF expression and neuroprotection and improves locomotor recovery after spinal cord injury. J Neurosurg. 121:1514-1525,2014.PDF
  18. Yaoita N, Shirakawa R, Fukumoto Y, Sugimura K, Miyata S, Miura Y, Nochioka K, Miura M, Tatebe S, Aoki T, Yamamoto S, Satoh K, Kimura T, Shimokawa H, Horiuchi H. Platelets are highly activated in patients of chronic thromboembolic pulmonary hypertension (CTEPH). Arterioscler Thromb Vasc Biol. 34:2486-2494,2014.PDF
2013年
  1. Eba S, Hoshikawa Y, Moriguchi T, Mitsuishi Y, Satoh H, Ishida K, Watanabe T, Shimizu T, Shimokawa H, Okada Y, Yamamoto M, Kondo T. The nuclear factor erythroid 2-related factor 2 activator oltipraz attenuates chronic hypoxia-induced cardiopulmonary alterations in mice. Am J Respir Cell Mol Biol. 49:324-333,2013.PDF
  2. Fukumoto Y, Yamada N, Matsubara H, Mizoguchi M, Uchino K, Yao A, Kihara Y, Kawano M, Watanabe H, Takeda Y, Adachi T, Osanai S, Tanabe N, Inoue T, Kubo A, Ota Y, Fukuda K, Nakano T, Shimokawa H. Double-blind, placebo-controlled clinical trial with a Rho-kinase inhibitor in pulmonary arterial hypertension -A pilot efficacy trial- Circ J. 77:2619-2625,2013.PDF
  3. Shimizu T, Fukumoto Y, Tanaka S, Satoh K, Ikeda S, Shimokawa H. Crucial role of ROCK2 in vascular smooth muscle cells for hypoxia-induced pulmonary hypertension in mice. Arterioscler Thromb Vasc Biol. 33:2780-2791,2013.PDF
  4. Sugimura K, Fukumoto Y, Miura Y, Nochioka K, Miura M, Tatebe S, Aoki T, Satoh K, Yamamoto S, Yaoita N, Shimokawa H. Three-dimensional-optical coherence tomography imaging of chronic thromboembolic pulmonary hypertension. Eur Heart J. 34:2121,2013.PDF
  5. Suzuki H, Sumiyoshi A, Kawashima R, Shimokawa H. Diffrenet brain activation under left and right ventricular stimulation: An fMRI study in anesthetized rats. PLoS One 2013;8(2):e56990.PDF
  6. Tatebe S, Fukumoto Y, Sugimura K, Miura Y, Nochioka K, Aoki T, Miura M, Yamamoto S, Yaoita N, Satoh K, Shimokawa H. Optical coherence tomography is superior to intravascular ultrasound for diagnosis of distal-type chronic thromboembolic pulmonary hypertension. Circ J. 77:1081-1083,2013.PDF
2012年
  1. Aizawa K, Yasuda S, Takahashi J, Takii T, Kikuchi Y, Tsuburaya R, Ito Y, Ito K, Nakayama M, Takeda M, Shimokawa H. Involvement of Rho-kinase activation in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in patients with coronary artery disease. Circ J. 76:2552-2560,2012.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. 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
  5. Sugimura K, Fukumoto Y, Satoh K, Nochioka K, Miura Y, Aoki T, Tatebe S, Miyamichi-Yamamoto S, Shimokawa H. Percutaneous transluminal pulmonary angioplasty markedly improves pulmonary hemodynamics and long-term prognosis in patients with chronic thromboembolic pulmonary hypertension. Circ J. 76:485-488,2012.PDF
  6. 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
2011年
  1. Fukumoto Y, Shimokawa H. Recent progress in the management of pulmonary hypertension. Circ J. 75:1801-1810,2011. (Review)PubMed
  2. 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.PubMed
  3. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy for ischemic cardiovascular disorders. Am J Cardiovasc Drugs. 11:295-302,2011.PubMed
  4. 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
  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.PubMed
  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.PubMed
2010年
  1. Ito Y, Ito K, Shiroto T, Tsuburaya R, Gao JY, 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
  2. Ito K, Kagaya Y, Shimokawa H. Thyroid hormone and chronically unloaded hearts. Vascul Pharmacol. 52:138-141,2010.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. Takii T, Yasuda S, Takahashi J, Ito K, Shiba N, Shirato K, Shimokawa H; MIYAGI-AMI Study Investigators. Trends in acute myocardial infarction incidence and mortality over 30 years in Japan: report from the MIYAGI-AMI Registry Study. Circ J. 74:93-100,2010.PubMed
  5. 伊藤健太,下川宏明 : 体外衝撃波を用いた非侵襲性血管新生療法. 日本内科学会雑誌 99:2846-2852,2010.
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. 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
  3. Takagi Y, Yasuda S, Takahashi J, Takeda M, Nakayama M, Ito K, Hirose M, Wakayama Y, Fukuda K, Shimokawa H. Importance of dual induction tests for coronary vasospasm and ventricular fibrillation in patients surviving out-of-hospital cardiac arrest. Circ J. 273:767-769,2009.PubMed
2008年
  1. Oi K, Fukumoto Y, Ito K, Uwatoku T, Abe K, Hizume T, Shimokawa H. Extracorporeal shock wave therapy ameliorates hindlimb ischemia in rabbits. Tohoku J Exp Med. 214:151-158,2008.PubMed
  2. Shimokawa H, Ito K, Fukumoto Y, Yasuda S. Extracorporeal cardiac shock wave therapy for ischemic heart disease. Shock Waves. 17:449-455,2008.
  3. 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
  4. Ulrich M, Petre A, Youhnovski N, Promm F, Schirle M, Schumm M, Pero RS, Doyle A, Checkel J, Kita H, Thiyagarajan N, Acharya KR, Schmid-Grendelmeier PS, Simon HU, Schwart H, Tsutsui M, Shimokawa H, Bellon G, Lee J, Przybyski M, Doring G. Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase. J Biol Chem. 283:28629-28640,2008.PDF
2007年
  1. 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
  2. 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
  3. 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
  4. Yasuda S, Ikuta K, Uwatoku T, Oi K, Abe K, Hyodo F, Yoshimitsu K, Sugimura K, Utsumi H, Katayama Y, Shimokawa H. In vivo magnetic resonance imaging of atherosclerotic lesions with a newly developed Evans blue-DTPA-gadolinium contrast medium in apolipoprotein-E-deficient mice. J Vasc Res. 45:123-128,2007.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
2004年
  1. 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. 110:3055-61,2004.PubMed

(文責:伊藤健太)

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