2003 Fiscal Year Final Research Report Summary
The role of caveolin in pathogenesis of arteriosclerosis
| Project/Area Number |
13670735
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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 |
Circulatory organs internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
KIHARA Minoru Yokohama-City University, Internal Medicine II, Assistant professer, 医学部, 講師 (60177904)
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| Co-Investigator(Kenkyū-buntansha) |
TOYA Yoshiyuki Yokohama City University, Internal Medicine II, Associated Professer, 医学部附属病院, 助教授 (30237143)
UMEMURA Satoshi Yokohama City University, Internal Medicine II, Professer, 医学研究科, 教授 (00128589)
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| Project Period (FY) |
2001 – 2003
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| Keywords | caveolin / eNOS / renin-angiotensin system / ahterosclerosis |
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| Research Abstract |
Caveolin is a major component of caveolae, flask-shaped invaginations of plasma membranes that play important roles in the transmembrane signal transduction. This molecule functions as an endogenous negative regulator of endothelial-type nitric oxide synthase (eNOS). Recently, caveolin has been implicated in the inhibitory regulation of cell proliferation. The present study investigated the expression of caveolin and eNOS in the arterial hyperplastic lesion. We found that angiotensinogen gene-knockout (Atg-/-) mice had renal arteriosclerosis-like lesion especially in the interlobular arteries and afferent arteriolesis. In these lesion, caveolin was overexpressed whereas eNOS expression was strongly suppressed. After 10-days salt loading (4% NaCl diet), caveolin expression was significantly decreased with an increase in eNOS expression. Hydralazine treatment almost completely abolished the effects of high-salt diet on cavelin and eNOS expression. These chnages were not found in other organs including liver, heart, spleen, lung, and skeletal muscles. Wild-type mice showed no changes in caveolin or eNOS expression during the treatment. A Dahl-salt sensitive rat was used as another model for hyperplastic renal arteriosclerosis. After 18-weeks of salt loading (8% NaCl diet), Dahl-salt sensitive rats showed sclerotic changes in the renal resistance vessels. The lesion inluded overexpression of caveolin and marked decreases in eNOS activity. On the other hand, Dahl-salt resistant rats did not show any changes in renal vasculature. These results were consistent with the idea that caveolin participates in vascular hyperplastic change through eNOS regulation especially in the condition where renin-angiotensinsystem is suppressed.
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