2011 Fiscal Year Final Research Report
The pivotal role of eNOS uncoupling-induced vascular endothelial dysfunction in cardiovascular diseases
| Project/Area Number |
22790712
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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 | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | 循環器学 / 血管内皮機能 |
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| Research Abstract |
We previously reported that eNOS uncoupling-induced vascular endothelial dysfunction is closely associated with diastolic heart failure(DHF) in salt-sensitive hypertensive rats. In this study, first, we found that angiotensin II induced eNOS uncoupling via ASK-1 activation and downregulation of GTPCH-I(BH4 producing enzyme) in vitro. Second, in clinical study, we found that peripheral endothelial dysfunction assessed by digital peripheral arterial tonometry, was significantly impaired in human DHF patients. Furthermore, blood BH4 levels tended to be decreased in DHF patients, indicating the involvement of eNOS uncoupling by BH4 downregulation also in human DHF.
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