Role of mast Cell chymase in the development of pulmonary hypertension associated with congenital heart diseases
Project/Area Number |
09670785
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Chiba University Shcool of Medicine |
Principal Investigator |
TERAI Masaru Terai, M.Chiba University School of Medicine, Separtment of Pediatrics, Lecturer, 医学部, 講師 (80207472)
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Project Period (FY) |
1997 – 1998
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Project Status |
Completed (Fiscal Year 1998)
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Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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Keywords | mast cell / chymase / angiotensin II / pulmonary hypertension / congenital heart disease / venttricular septal defect / chymase-angiotensin system / アンギオテンシン / キマ-ゼ |
Research Abstract |
The molecular mechanism involved in pulmonary vascular disease (PVD) associated with congenital heart disease (CHD) remains uncertain. Evidence suggesting that angiotensin converting enzyme plays an important role in pulmonary vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to the development of PVD in CHD.Twenty-three patients ranging from age 3 months to 45 years with atrial or ventricular or both septal defects with increased pulmonary arterial blood flow and pressure, with pulmonary vascular resistance ranging from 1.3 to 8.1 unit m^2, were studied. Mast cells and mast cell chymase were immunohistochemically identified in the lung biopsy tissues obtained during corrective surgery. There was a significant difference in numbers of total mast cells between patients (n=23) and controls (n=10) with normal pulmonary circulation (p<0.01). Moreover, chymase-containing mast cells in the lung tissues of CHD patients showed striking differences from those of controls. In the patients, 72% of lung mast cells contained chymase, compared to only 15% in controls (p<0.000l). Chymase-containing mast cells predominantly appeared in the media and adventitia of vessel walls. Importantly, angiotensin II was immunohistochemically detected in perivascular lesions where chymase was present, but not in the lesions where chymase was sparsely seen. Furthermore, the number of chymase-containing mast cells was correlated with pulmonary vascular resistance (r=0.64). These findings suggest a possible role of mast cell chymase in the development of early-stage PVD in CHD patients.
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Report
(3 results)
Research Products
(17 results)
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[Publications] Kimura H, Kasahara Y, Kurosu K, Sugito K, Takiguchi Y, Terai M, Mikata A, Natsume M, Mukaida N, Matsushima K, Kuriyama T: "Alleviation of monocrotaline-induced pulmonary hypertesion by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1" Lab Invest. 78. 571-578 (1998)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Publications] Kimura H,Kasahara Y,Kurosu K,Sugito K,Takiguchi Y,Terai M,Mikata A,Natsume M,Mukaida N,Matsushima K,Kuriyama T: "Alleviation of monocrotaline-induced pulmonary hypertesion by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1." Lab Invest. 78. 571-578 (1998)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Kimura H,Kasahara Y,Kurosu K,Sugito K,Takiguchi Y,Terai M,Mikata A,Natsume M,Mukaida N,Matsushima K,Kuriyama T: "Alleviation of monocrotaline-induced pulmonary hypertesion by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1." Lab Invest. 78. 1998 (571-578)
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