2010 Fiscal Year Final Research Report
Role of asymmetric dimethylarginine in cardio-renal syndrome
| Project/Area Number |
20590969
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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 |
Kidney internal medicine
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| Research Institution | Kurume University |
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Principal Investigator |
UEDA Seiji Kurume University, 医学部, 准教授 (80322593)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 慢性腎臓病 / 心腎連関 / 酸化ストレス / ADMA |
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| Research Abstract |
In recent years, increasing evidence has been shown that chronic kidney disease (CKD) is a strong cardiovascular risk factor, and therefore, the concept 'Cardio-Renal Syndrome (CRS)' is well recognized. One possible factor that could explain this link seems to be endothelial dysfunction (ED), which plays important roles in initiation and progression of atherosclerosis as well as progression of CKD. In this study, we investigated the roles of asymmetric dimethylarginine (ADMA), a causative factor for ED in CRS. In CKD patients, plasma levels of ADMA were increased as CKD stage progressed. Further, increased ADMA levels were significantly associated with PWV and LV mass index, surrogate markers for cardiovascular disease in these patients. In addition, ADMA levels were significantly related to the degree of glomerulosclerosis and interstitial fibrosis as well as annual reduction rates of GFR in biopsy-proven chronic glomerulonephritis patients. Animal models of CKD revealed that oxidative stress and/or ER stress-mediated dysregulation of DDAH, an enzyme for ADMA could account for ADMA elevation in CKD. Reduction of ADMA levels by DDAH gene transfer in CKD models not only ameliorated ED but also blocked the development of renal injury. ADMA is a potent endogenous NOS inhibitor and its accumulation may play important roles in ED, thereby contributing to the development and progression of cardiovascular disease and renal injury in patients with CKD. Countering of ADMA by enhancement of DDAH activity may be novel strategies or preventing the cardiorenal complications in patients with CKD.
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[Journal Article] Circulating levels of advanced glycation end products (AGE) and interleukin-6 (IL-6) are independent determinants of serum asymmetric dimethylarginine (ADMA) levels in patients with septic shock.2009
Author(s)
Nakamura T, Sata E, Fujiwara N, Kawagoe Y, Suzuki T, Ueda Y, Yamada S, Shoji H, Takeuchi M, Matsui T, Ueda S, Adachi H, Okuda S, Yamagishi S.
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Journal Title
Pharmacol.Res. 60
Pages: 515-518
Peer Reviewed
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[Journal Article] Positive association of serum levels of advanced glycation end products (AGEs) and high mobility group box-1 (HMGB-1) with asymmetric dimethylarginine (ADMA) in non-diabetic chronic kidney disease patients.2009
Author(s)
Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Ueda Y, Suzuki T, Yamada S, Takeuchi M, Fukami K, Ueda S, Adachi H, Matsui T, Okuda S, Yamagishi S.
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Journal Title
Metabolism 58
Pages: 1624-1628
Peer Reviewed
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[Journal Article] Involvement of asymmetric dimethylarginine (ADMA) in tubulointerstitial ischemia in early phase of diabetic nephropathy.2009
Author(s)
Shibata R, Ueda S, Yamagishi S, Kaida Y, Matsumoto Y, Fukami K, Hayashida A, Matsuoka H, Kato S, Kimoto M, Okuda S.
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Journal Title
Nephrol Dial Transplant. 24
Pages: 1162-1169
Peer Reviewed
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