2011 Fiscal Year Final Research Report
Role of Protein Quality Control in Cardiac Remodeling
| Project/Area Number |
22790697
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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 | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | 心不全 / 心肥大 / シグナル伝達 |
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| Research Abstract |
Under condition of increased hemodynamic load, cardiomyocytes undergo hypertrophy to adapt to increased work load and reduce wall stress. But, the prolonged existence of cardiac hypertrophy is an independent risk factor for cardiac morbidity and mortality. Here, we investigated the role of muscle atrophy F-box(MAFbx/atrogin-1), an E3 ubiquitin ligase, in regulating cardiac hypertrophy and function in response to pressure overload. Transverse aortic constriction(TAC)-andβ.-adrenergic-induced increases in cardiac hypertrophy and lung congestion were significantly smaller in MAFbx knockout(KO) than in wild-type(WT) mice. Downregulation of MAFbx inhibits cardiac hypertrophy in part through stabilization of I. B and inactivation of nuclea factor-. B. Inhibition of MAFbx attenuates pathological hypertrophy, thereby protecting the heart from progression into heart failure.
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