2016 Fiscal Year Final Research Report
Effect of hyperhomocysteinemia on vascular dysfunction in renal failure
| Project/Area Number |
26460207
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
ICHIDA Kimiyoshi 東京薬科大学, 薬学部, 教授 (80183169)
NAKAMURA Makiko 東京薬科大学, 薬学部, 助教 (80447557)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | ホモシステイン / メチオニン / 腎不全 / 代謝フラックス / GC-MS / 安定同位体 / 血管内皮 / 血管平滑筋 |
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| Outline of Final Research Achievements |
Chronic kidney disease (CKD) and hyperhomocysteinemia are risk factors of cardiovascular disease individually. While the association of CKD and hyperhomocysteinemia is well established in clinical populations, little is known about the role of hyperhomocysteinemia in the development of vascular dysfunction of CKD. This study is conducted to clarify how plasma homocysteine (Hcy) is elevated in CKD and the effects of hyperhomocysteinemia on vascular function in CKD. We determined the turn over rates for Hcy production and disposal of 5/6 nephrectomized rats using a stable isotope technique and showed that decreased remethylation of Hcy to methionine (Met) was associated with hyperhomocysteinemia in CKD. Using 5/6 nephrectomized rats with hyperhomocysteinemia induced by Met-enriched diets, vasodilataions of thoracic aorta were determined. Combination of hyperhomocysteinemia and CKD resulted in impairments of both endothelium-dependent and endothelium-independent vasodilatations.
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| Free Research Field |
医歯薬学
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