| Project/Area Number |
16390217
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIRATA Yasunobu The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (70167609)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Etsu The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (40313134)
SATA Masataka The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (80345214)
NISHIMATSU Hiroaki The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60251295)
NAGANO Tstsuo The University of Tokyo, Pharmaceutical Science, Professor, 薬学系研究科, 教授 (20111552)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | arterioscleosis / nitric oxide / fluorescence / endothelium / angiogenesis / 血管平滑筋 / サイトカイン / 脂肪細胞 / アデノウイルス / インスリン抵抗性 / 新生内膜 / ラット |
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| Research Abstract |
Endothelial dysfunction is frequently observed in diabetes (DM). However, the detailed mechanism for endothelial dysfunction in DM is still unclear. In DM, it has been reported that cytokines release from adipocytes such as TNF-α and IL-6 is augmented and that they induce vascular inflammation. In this study we study the role of endogenous cytokines in endothelial dysfunction in DM with using semapimod (Sem), an inhibitor of endogenous cytokines release. Male diabetic Zucker rats (12 weeks) were divided into lean (LZ), obese (OZ), and Sem (5mg/kg/day)-treated obese rats (OZ/Sem). After 4 weeks of treatment, endothelium dependent vasodilatory responses of thoracic aorta to acetylcholine (ACh) and adrenomedullin (AM) were examined. Furthermore, induction of Akt phosphorylation (p-Akt) of thoracic aorta which was stimulated with 10^<-7> of AM for 15 min was examined by Western blot analysis. Systolic blood pressure, blood glucose, and triglyceride were higher in OZ rats and Sem treatment had no effect on these parameters. Serum CRP level of OZ rats was higher compared to LZ rats and Sem significantly reduced its level. TNF-α, IL-1β, and IL-6 contents in various tissues were significantly greater in OZ rats than in LZ rats, whereas these increments were suppressed in OZ/Sem rats. Endothelium-dependent vasodilation by ACh and AM was significantly attenuated in OZ rats, and was improved by Sem treatment. Intraperitoneal administration of TNF-α markedly reduced ACh-evoked vasodilation in thoracic aorta of LZ rats. AM-induced p-Akt and cGMP production of thoracic aorta were significantly less in OZ rats compared to LZ rats. However, it was recovered by Sem treatment. In DM, endogenous cytokines play an important role in endothelial dysfunction and inhibition of these cytokines release may improve endothelial dysfunction.
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