| Project/Area Number |
18590804
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
YOSHIMOTO Takanobu Tokyo Medical and Dental University, Department of Clinical and Molecular Endocrinology, assistant professor (80297457)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | aldosterone / mineralocorticoid receptor / receptor / oxidative stress / renin-angiotensin system / 血管病態学 |
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| Research Abstract |
This study revealed several new physiological aspects of the molecular mechanisms of aldosterone-induced cardiovascular injury. We have demonstrated that Aldo directly upregulates ACE in cardiovascular tissue in aldosterone-induced hypertensive rats (Aldo-rats). ACE upregulation in cardiovascular tissue is involved in the activation of local RAS in Aldo-rats, which partly contributes to oxidative stress and inflammatory changes in cardiovascular tissue of Aldo rats. We have also shown that in cultured ECs Aldo induces of NADPH-oxidase-dependent superoxide generation via mineralocorticoid receptor (MR)-mediated Rac1 activation. In cultured mesagial cell, Aldo increased ICAM-1 and CTGF expression via SGK-1 mediated NFkB activation, and CTGF, ICAM-1, and SGK-1 immunoreactivities were increased in glomerular tissue from Aldo-rats. These results suggest that MR-mediated NADPH oxidase activation in vascular cells and local RAS activation via ACE upregulation compose "vicious cycle", thereby leading to the development of Aldo-induced cardiovascular injury, and that MR-mediated SGK-1-NFkB axis is involved in the renal injury caused by Aldo.
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