| Project/Area Number |
13670761
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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 |
Circulatory organs internal medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
IWASAKA Toshiji Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (00098120)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Hiroaki Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10239072)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | angiogenesis / stem cells / regenerative medicine / angiotensin / ARB / angiotensin receptor / アンジオテンシンII / AT1受容体 / AT2受容体 / HB-EGF |
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| Research Abstract |
Due to the discovery of nonpeptidic ligands the receptors for angiotensin(Ang) II are classified into two subtypes(AT1-R and AT2-R). AT1-R mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetus. Its expression is very low in the cardiovascular system of the adult. AT1-R signals stimulate HB-EGF release to activate EGF-R followed by the ERK signaling. This AT1R pathway enhances VEGF releases from myocytes or vascular smooth muscle cells and potenciates angiogenic response. In AT1R KO mice, collateral vessel formation was reduced and mobilization of endothelial progenitor cells was blunted. In AT2R KO mice, ATIR-mediated action was enhanced, comparable with anti-ATIR effect of AT2R. AT2-R activates the kinin/nitric oxide/cGMP system in the cardiovascular systems, resulting in AT2-R-mediated cardioprotection, vasodilation and pressure natriuresis. These effects, transmitted by AT2-R, are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in a Gi-protein-dependent manner. Thus, Ang II stimulates angiogenesis in ischemic lesions via AT1-R, suggesting that in acute myocardial infarction Ang II receptor blocker may attenuate collateral blood flow in acute pahase.
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