2006 Fiscal Year Final Research Report Summary
MOLECULAR MECHANISM OF ADIPONECTIN-DEFICIENCY ON HYPERTENSION AND CARDIVASCULAR REMODELING
| Project/Area Number |
17590960
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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 |
Endocrinology
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| Research Institution | Osaka University |
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Principal Investigator |
KIHARA Shinji OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT, 医学系研究科, 助手 (20332736)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Tadashi OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学系研究科, 講師 (90252668)
FUNAHASHI Tohru OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学系研究科, 助教授 (60243234)
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| Project Period (FY) |
2005 – 2006
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| Keywords | GENE / INTERNAL MEDICINE / CARDIOVASCULAR / HYPERTENSION / DIABETES MELLITUS / PROTEOME |
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| Research Abstract |
This study was designed to elucidate the molecular mechanism of hypoadiponectinemia on the development of hypertension and cardiovascular remodeling with adiponectin deficient mice. Adiponectin deficient mice developed hypertension when maintained on a high-salt diet without insulin resistance. The hypertension of salt-fed adiponectin deficient mice was associated with the impaired induction of endothelial NO synthase mRNA level in the systemic vasculature. Adiponectin therapy lowered the elevated blood pressure and increased endothelial NO synthase. Ischemia-reperfusion in adiponectin deficient mice resulted in increased myocardial infarct size. Administration of adiponectin diminished infarct size. Adiponectin suppressed myocardial apoptosis and tumor necrosis factor-alpha expression through AMP-activated protein kinase and cyclooxygenase pathways, respectively. In human aortic endothelial cells, adiponectin suppressed inflammatory cytokine IL-8 production, which may mediate adiponectin inhibition of atherosclerosis. In addition, as clinical significance of adiponectin, we found that 1) Angiotensin II type-1 receptor blocker increased plasma adiponectin level by targeting oxidative stress in adipose tissue, 2) Smoking habit was associated decreased adiponectin level, and oxidative stress and nicotine reduced adiponectin mRNA in adipocytes, 3) Thiazolidinedione treatment improved left ventricular diastolic function without left ventricular mass regression in hypertensive patients in proportion to the amelioration of insulin resistance, 4) Adiponectin was decreased in patients with peripheral arterial occlusive disease in proportion to the severity of the disease, 5) Renal function was a significant regulator of adiponectin when categorized by chronic kidney disease stages, whereas hypoadiponectinemia was a predictor of cardiovascular disease. These results provide an adiponectin mediated novel molecular basis of hypertension and cardiovascular remodeling.
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Research Products
(16 results)
