| Project/Area Number |
11838004
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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 Institution | Fukui Medical University |
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Principal Investigator |
MIYAMORI Isamu Faculty of Medicine Fukui Medical University Professor, 医学部, 教授 (40142278)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Haruhiko Faculty of Medicine Fukui Medical University Assistant, 医学部・附属病院, 助手 (40303375)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Aldosterone / angiotensin II / PCR-RT / 鉱質コルチコイド / CYP11B2 / 肺動脈血管細胞 / 血管平滑筋細胞 / 動脈硬化 / ステロイドホルモン / 高血圧 / 血管細胞 |
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| Research Abstract |
Aldosterone and other mineralocorticoids are synthesized in the cardiovascular tissues. In the genetically hypertensive rat, aldosterone synthase genes (CYP11 B2) are expressed in the heart and up-regulated by angiotensin II (Ang II). Since aldosterone potentiates the hypertrophic effect of Ang II through mineralocorticoid receptors (MRs) which are present in the heart and vessels, it is suggested that the systemic and local renin-angiotensin-aldosterone system contribute to the cardiac hypertrophy in an accelerated fashion. Using PCR-RT we analyzed all enzymes involved in corticosteroids in human vascular cells cultivated from pulmonary arteries. Genes encoding these enzymes were detected with the exception of cholesterol side chain cleavage and 11β-hydroxylase genes. Thus aldosterone may be synthesized from the circulating precursor steroids in vascular cells, which is different from the steroidogensis in the adrenal cortex. CYP11B2 expression in both endothelial cells and smooth muscle cells is stimulated by 10-9 M Ang II, supporting the role of aldosterone for Ang II induced vascular remodeling. In spite of these evidence in arteries, the existence and functional role of local aldosterone is controversial in the human heart. Positive immunohistochemical staining of MRs in the failling human adult heart favors the clear role of aldosterone in such circumstances regardless of whether it is synthesized in the adrenal or in the heart.
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