| Project/Area Number |
25670396
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Keio University |
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Principal Investigator |
SANO Motoaki 慶應義塾大学, 医学部, 准教授 (30265798)
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| Project Period (FY) |
2013-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 循環器・高血圧 / 細胞・組織 / 分析科学 / 心不全 / 副腎 / レニン・アンジオテンシン系 / 虚血 / アルドステロン |
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| Research Abstract |
Chronic salt overload in Dahl-salt sensitive rats stimulates aldosterone production via local activation of renin-angiotensin system (RAS). Beta3-adrenergic receptor was highly upregulated concomitant with the progression of cardio-renal injury. Adrenal glands became hypoxic as cardio-renal injury progress and both hypoxia induced the expression of beta3-adrenergic receptor via HIF activation in adrenocortical cells. Macrophages were infiltrated in the adrenal cortex in rats with cardio-renal injury and macrophage ablation reduced aldosterone production. Co-culture with macrophages or a supernatant of macrophages stimulated CYP11B2 expression in adrenocortical cells. Acquisition of catecholamine-responsiveness via the induction of beta3-adrenergic receptor under tissue ischemic and crosstalk between macrophages and adrenocortical cells accounts for the RAS-independent aldosterone production associated with cardio-renal injury.
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