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The role of caveolin in pathogenesis of arteriosclerosis

Research Project

Project/Area Number 13670735
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionYokohama City University

Principal Investigator

KIHARA Minoru  Yokohama-City University, Internal Medicine II, Assistant professer, 医学部, 講師 (60177904)

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)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordscaveolin / eNOS / renin-angiotensin system / ahterosclerosis / カベリオン / レニンアンジオテンシン系 / 血管内皮 / eNOS / レニン・アンジオテンシン系
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.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] Hashimoto T et al.: "Lipoxygenase products regulate nitric oxide and inducible nitric・・・・・・"Hypertens Res. 26. 177-184 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato K et al.: "Expression of endothelial nitric oxide synthase in renal tissues of angiotensin type-1a receptor gene-knockout mice"J Am Soc Nephrol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hashimoto T, Kihara M, Yokoyama K, Fujita T, Kobayashi S, Matsushita K, Tamura K, Hirawa N, Toya Y, Umemura S.: "Lipoxygenase products regulate niric oxide and inducibel nitric oxide synthase production in interleukin-1β stimulated vascular smooth muscle cells."Hypertens Res. 26. 177-184 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato K, Kihara M, Hashimoto T, Matsushita K, Koide Y, Tamura K, Hirawa N, Toya Y, Fukamizu A, Umemura S.: "Expression of endothelial nitric oxide synthase in renal tissues of angiotensin type-1a receptor gene-knockout mice."J Am Soc Nephrol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hashimoto T et al.: "Lipoxygenase products regulate nitric oxide and inducible nitric……"Hypertens Res. 26. 177-184 (2002)

    • Related Report
      2003 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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