Project/Area Number |
23792094
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Emergency medicine
|
Research Institution | Kurume University |
Principal Investigator |
OBA Toyoharu 久留米大学, 医学部, 助教 (10389257)
|
Project Period (FY) |
2011 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | シグナル伝達、 / 心筋保護 / 、サイトカイン、 / 神経調節、 / 臓器連関 / シグナル伝達 / サイトカイン / 神経調節 / 心筋虚血 / プレコンディショニング / 腎血流 / 腎神経 |
Research Abstract |
Remote ischemic preconditioning (RIPC) induced by brief episodesof blood flow occlusion applied in limbs is a powerful innate mechanism of cardiacprotection against ischemia. Mechanisms for the cardiac RIPC have not been fullyelucidated. Here we propose a novel mechanism of RIPC; renal nerve plays an importantrole in cardioprotection after myocardial infarction (MI) by releasing erythropoietin(EPO) production from the kidney. In mice transient limb ischemia decreased renal bloodflow (RBF), upregulated hypoxia-inducible factor-1α (HIF1α) and EPO mRNA in the kidney,and increased the plasma EPO level. Transient limb ischemia activated cardioprotectivesignaling pathways and anti-apoptotic pathways in the heart, and reduced infarct size,which were abolished by administration of an EPO neutralizing antibody. Renal nerve denervation also abolished the transient limb ischemia-induced RBF reduction, EPOproduction, and cardioprotection. In humans, Transient limb ischemia of the upper armdecreased RBF and increased plasma EPO levels. Taken together, our data suggest thatcardioprotection by transient limb ischemia is produced through renal nerve?mediatedreduction of RBF associated with activation of the HIF1α-EPO pathway.
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