| Project/Area Number |
20790536
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyushu University |
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Principal Investigator |
TAKEDA Kotaro Kyushu University, 医学研究院, 客員助教 (50467908)
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| Research Collaborator |
ICHIKI Toshihiro 九州大学, 医学研究院, 客員准教授 (80311843)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 分子血管病態学 / 低酸素シグナル / PHD / PHD阻害剤 / 炎症 / アンジオテンシン受容体 / HIF / 低酸素 |
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| Research Abstract |
Ischemic diseases such as heart attack and stroke are important cause of death in the developed courtiers including Japan. Therefore, it is an urgent need to find the clue for the diseases and to establish the novel treatment strategy. Our body has a sophisticated system to adapt hypoxic/ischemic condition by inducing angiogenesis and erythrocytosis. Prolyl hydroxylase (PHD)2 is a key sensor for oxygen concentration and a negative regulator for hypoxia inducible factor (HIF) expression. This oxygen sensing system play a key role to adapt hypoxic/ischemic insults, thus modification of the system has gained an attention as a potential strategy. In this project, we studied that the modification of hypoxia pathway could be serve as a cardioprotective way by regulating angiogenesis, inflammation and renin-angiotensin system. We have developed endothelial cell-specific, vascular smooth muscle cell-specific, and cardiomyocyte-specific PHD2 knockout mice. While we did not find any significant angiogenic response in these mice, systemic PHD2 knockout mice did show significant angiogenesis, suggesting that some systemic factors mediate to induce angiogenesis. PHD inhibitors treatment suppresses acute inflammatory responses in cultured macrophages. PHD inhibitors also suppressed angiotensin II type 1 receptor expression in cultured vascular smooth muscle cells. Collectively, PHD2 regulates angiogenesis, inflammation and renin-angiotensin system, and hence has a great potential for the treatment of cardiovascular diseases.
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