| Project/Area Number |
20590884
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松原 弘明 京都府立医科大学, 医学研究科, 教授 (10239072)
沢田 尚久 京都府立医科大学, 医学研究科, 講師 (00315938)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | ストレス / PYK2 / チロシンキナーゼ / 活性酸素 / 血管生物学 / チロシンキナーぜ |
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| Research Abstract |
We have clarified that various cardiovascular stress activates tyrosine kinase PYK2.The activated PYK2 subsequently produce Reactive Oxygen Species(ROS) production and the ROS promotes cardiovascular inflammation, leading to many cardiovascular disease such as atherosclerosis, cardiovascular remodeling after myocardial ischemia and pressure-overload by aortic banding, neointimal hypertrophy after endothelial damages. In this study, we studied whether inhibition of PYK2 in vivo may attenuate the cardiovascular diseases in mice model. We intravenously introduced PYK2-shRNA into mice to knockdown PYK2 in vivo. Expression levels of PYK2 in heart, aorta and kidney decreased less than 30% of the control. Then, 14 days after introducing shRNA for PYK2, the mice was conducted the cardiovascular injury model described above. We observed that endothelial injury by guide wire, hypercholesterolemia under Apo-E deficiency, medial hypertrophy after Angiotensin-II infusion, myocardial hypertrophy after aortic banding was markedly attenuated. Thus, PYK2 is novel and potential therapeutic target of various cardiovascular diseases.
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