The participation of C-C chamomkine, MCP-1, in the development of pulmonary vascular remodeling in patients with chronic thromboembolic pulmonary hypertension.
| Project/Area Number |
12670547
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nara Medical university (2001)
Chiba University (2000) |
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Principal Investigator |
KIMURA Hiroshi Nara Medical University School of Medicine, Professor, 医学部, 教授 (20195374)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Nobihiro Chiba University Hospital, Assistant Professor, 医学部・附属病院, 講師 (40292700)
寺井 勝 千葉大学, 医学部・附属病院, 講師 (80207472)
中島 伸之 千葉大学, 医学部, 教授 (40241947)
栗山 喬之 千葉大学, 医学部, 教授 (20009723)
滝口 裕一 千葉大学, 医学部・附属病院, 助手 (30272321)
岡田 修 千葉大学, 医学部・附属病院, 講師 (60177045)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Pulmonary hypertension / Pulmonary thromboembolism / Pulmonary vascular remodeling / C-C chemokine / Macrophages / Immunohistochemical staining / 単球 / 肺血管抵抗 |
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| Research Abstract |
The pathogenesis and molecular mechanisms of vascular remodeling causing chronic thromboembolic pulmonary hypertension (CTEPH) have not been well clarified. Recently, it has been elucidated that monocyte chemo attractant protein-1 (MCP-1), a C-C chamomile, play important roles in the development of congestive heart failure. We, therefore, hypothesized that MCP-1 may be involved in the mechanism of pulmonary vascular remodeling caused by CTEPH because most patients receive strong shear stress in the pulmonary vascular wall as well as in the right ventricle. Circulating levels of MCP-1 was measured by sandwich ELISA in CTEPH patients. Simultaneously, pathological specimens in the organized initial thrombosis lesions as well as in the lung biopsy obtained from the patients with CTEPH undergoing thromboendarterectomy were investigated. The plasma level of MCP-1 was significantly correlated with pulmonary vascular resistance in patients with the thromboemboli showing central predominant pattern. Pathological specimens demonstrated immunoreactivity of MCP-1 in endothelium, smooth muscle cells and macrophages within neointima in the hypertensive large elastic pulmonary artery. The expression of MCP-1 as well as CCR2, chamomile receptors of MCP-1, was observed in the remodeling sites of pulmonary arterioles. It is suggested that increased homodynamic in the pulmonary vasculature may potentially activate pulmonary arterial endothelial cells, smooth muscle cells and macrophages, resulting in up regulation of plasma MCP-1 level through shear stress in CTEPH. These findings demonstrate that MCP-1 produced in the neointima of thromboembolic lesion can essentially take part in the pathogenesis of the vascular remodeling in the pulmonary arterioles in patients with CTEPH.
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Report
(3 results)
Research Products
(9 results)
