Right ventricular fibrosis/ Rho-kinase pathway in the development of right heart failure
Project/Area Number |
25461100
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | Kurume University (2014-2015) Tohoku University (2013) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
Shimokawa Hiroaki 東北大学, 大学院医学系研究科, 教授 (00235681)
Satoh Kimio 東北大学, 学内共同利用施設等, 准教授 (80436120)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 右心不全 / 右室線維化 / Rhoキナーゼ / 内皮型一酸化合成酵素 / コラーゲン代謝 / 内皮型一酸化窒素合成酵素 |
Outline of Final Research Achievements |
Pulmonary hypertension (PH) finally causes right ventricular (RV) failure. We examined the mechanisms of RV remodeling in PH. In human RV autopsy samples, RV failure was associated with RV hypertrophy, interstitial and perivascular fibrosis, decreased capillary density and increased macrophage recruitment. Further, perivascular MMP2 and Rho-kinase activity were increased in PH patients. In animals, both hypoxic ndothelial nitric oxide synthase-deficient (eNOS-/-) and collagenase-resistant knock-in (ColR/R) mice developed greater extent of RV hypertrophy, perivascular remodeling and macrophage infiltration compared with WT mice. ColR/R mice were able to increase their capillary density in the RV in response to hypoxia. Both mouse models showed increased Rho-kinase activation. RV remodeling occurs early during PH development through fibrosis, perivascular remodeling, and capillary rarefaction, in which eNOS pathway and collagen metabolism can be new therapeutic targets.
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Thrombin-activatable fibrinolysis inhibitor in chronic thromboembolic pulmonary hypertension.2016
Author(s)
Yaoita N, Satoh K, Satoh T, Sugimura K, Tatebe S, Miyamichi-Yamamoto S, Aoki T, Miura M, Miyata S, Kawamura T, Horiuchi H, Fukumoto Y, Shimokawa H.
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: in press
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Multiple Beneficial Effects of Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension2016
Author(s)
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.
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Journal Title
Circulation Journal
Volume: 80
Issue: 4
Pages: 980-988
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders.2015
Author(s)
Yatsuga S, Fujita Y, Ishii A, Fukumoto Y, Arahata H, Kakuma T, Kojima T, Ito M, Tanaka M, Saiki R, Koga Y.
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Journal Title
Ann Neurol
Volume: 78
Issue: 5
Pages: 814-823
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Long-term safety and efficacy of imatinib in pulmonary arterial hypertension.2015
Author(s)
Frost AE, Barst RJ, Hoeper MM, Chang HJ, Frantz RP, Fukumoto Y, Galié N, Hassoun PM, Klose H, Matsubara H, Morrell NW, Peacock AJ, Pfeifer M, Simonneau G, Tapson VF, Torres F, Dario Vizza C, Lawrence D, Yang W, Felser JM, Quinn DA, Ghofrani HA.
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Journal Title
J Heart Lung Transplant
Volume: 34
Issue: 11
Pages: 1366-1375
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ezetimibe combined with standard diet and exercise therapy improves insulin resistance and atherosclerotic markers in patients with metabolic syndrome.2015
Author(s)
Ohbu-Murayama K, Adachi H, Hirai Y, Enomoto M, Fukami A, Obuchi A, Yoshimura A, Nakamura S, Nohara Y, Nakao E, Umeki Y, Fukumoto Y.
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Journal Title
J Diabetes Investig
Volume: 6
Issue: 3
Pages: 325-333
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues by FDG-PET/CT.2015
Author(s)
Tahara N, Yamagishi SI, Kodama N, Tahara A, Honda A, Nitta Y, Igata S, Matsui T, Takeuchi M, Kaida H, Kurata S, Abe T, Fukumoto Y.
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Journal Title
J Clin Endocrinol Metab
Volume: in press
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Plasma renin activity and resting heart rate in a population of community-dwelling Japanese: The Tanushimaru Study.2015
Author(s)
Adachi H, Enomoto M, Fukami A, Kumagai E, Nakamura S, Yoshimura A, Obuchi A, Hori K, Nohara Y, Nakao E, Fukumoto Y.
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Journal Title
Am J Hypertens
Volume: in press
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Association of serum eicosapentaenoic acid to arachidonic acid ratio with microalbuminuria in a population of community-dwelling Japanese.2015
Author(s)
Fukami A, Adachi H, Hirai Y, Enomoto M, Otsuka M, Kumagai E, Nakamura S, Yoshimura A, Obuchi A, Nohara Y, Nakao E, Hori K, Fukumoto Y.
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Journal Title
Atherosclerosis
Volume: 239
Issue: 2
Pages: 577-582
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Noninvasive evaluation of bone-forming activity within the calcified atherosclerotic lesions by Tc 99m HMDP scintigraphy.2015
Author(s)
Tahara N, Tahara A, Honda A, Nitta Y, Igata S, Nakamura Y, Takeuchi Y, Akashi H, Tanaka H, Morioka M, Narula J, Yamagishi SI, Fukumoto Y.
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Journal Title
JACC Cardiovasc Imaging
Volume: 8
Issue: 1
Pages: 108-109
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Crucial role of Rho-kinase in pressure overload-induced right ventricular hypertrophy and dysfunction in mice.2014
Author(s)
Ikeda S, Satoh K, Kikuchi N, Miyata S, Suzuki K, Omura J, Shimizu T, Kobayashi K, Kobayashi K, Fukumoto Y, Sakata Y, Shimokawa H.
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] Enhanced [18F]fluorodeoxyglucose accumulation in the right ventricular free wall predicts long-term prognosis of patients with pulmonary hypertension: a preliminary observational study.2014
Author(s)
Tatebe S, Fukumoto Y, Oikawa-Wakayama M, Sugimura K, Satoh K, Miura Y, Aoki T, Nochioka K, Miura M, Yamamoto S, Tashiro M, Kagaya Y, Shimokawa H.
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Journal Title
Eur Heart J Cardiovasc Imaging
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] Impact of physical activity on cardiovascular events in patients with chronic heart failure2013
Author(s)
Miura Y, Fukumoto Y, Miura T, Shimada K, Asakura M, Kadokami T, Ando SI, Miyata S, Sakata Y, Daida H, Matsuzaki M, Yasuda S, Kitakaze M, Shimokawa H.
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Journal Title
Circ J
Volume: 77
Pages: 2963-2972
Related Report
Peer Reviewed
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[Journal Article] A double-blind, placebo-controlled clinical trial with a Rho-kinase inhibitor in pulmonary arterial hypertension; a pilot efficacy trial.2013
Author(s)
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, Nakano T, Shimokawa H.
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Journal Title
Circ J
Volume: 77
Pages: 2619-2625
Related Report
Peer Reviewed
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[Journal Article] Rho-kinase activation in patients with heart failure.2013
Author(s)
Do E Z, Fukumoto Y, Sugimura K, Miura Y, Tatebe S, Yamamoto S, Aoki T, Nochioka K, Nergui S, Yaoita N, Satoh K, Kondo M, Nakano M, Wakayama Y, Fukuda K, Nihei T, Kikuchi Y, Takahashi J, Shimokawa H.
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Journal Title
Circ J
Volume: 77
Pages: 2542-2550
NAID
Related Report
Peer Reviewed
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[Journal Article] Optical coherence tomography is superior to intravascular ultrasound for diagnosis ofdistal-type chronic thromboembolic pulmonary hypertension.2013
Author(s)
Tatebe S, Fukumoto Y, Sugimura K, Miura Y, Nochioka K, Aoki T, Miura M, Yamamoto S, Yaoita N, Satoh K, Shimokawa H.
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Journal Title
Circ J
Volume: 77
Pages: 1081-1083
Related Report
Peer Reviewed
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