| Project/Area Number |
23790830
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 慢性心不全 / 慢性腎臓病 / エピジェネティックス / 臓器障害 / ミッドカイン / AKT / RSK |
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| Research Abstract |
Midkine is a heparin-binding growth factor having various functions such as cell growth,cell survival, and migration of inflammatory cells. We have previously reported thatserum midkine levels are independently associated with adverse cardiac events in patientswith heart failure. The aim of this study was to examine the role of midkine on thepathogenesis of the heart failure.
Midkine expression levels were mainly increased after transverse aortic constriction (TAC)surgery. We generated transgenic mice with cardiac specific overexpression of midkine(MK-Tg) using α-myosin heavy chain promoter. After TAC operation, phosphorylation ofextracellular signal-regulated kinase (ERK) 1/2 and AKT, and the expression levels of fetalgene in the heart were significantly increased in MK-Tg mice than in WT mice. The ratioof left ventricular weight to body weight and left ventricular end-diastolic dimension weresignificantly increased, and fractional shortening and maximum and minimum of leftventricular developed pressure were significantly decreased in MK-Tg mice than in WTmice after TAC operation. The degree of interstitial fibrosis and profibrotic geneexpressions were significantly higher in MK-Tg mice than in WT mice. Consistent withthese results, Kaplan-Meier analysis revealed that the survival rate in MK-Tg mice wassignificantly lower compared with WT mice. We concluded that cardiac overexpression ofMK plays a critical role in pressure overload induced cardiac hypertrophy and remodeling.
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