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2013 Fiscal Year Final Research Report

Is angiotensin II receptor activation involved in the mechanism and pathophysiological role of oxidized LDL?

Research Project

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Project/Area Number 23591102
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

YAMAMOTO Koichi  大阪大学, 医学(系)研究科(研究院), 講師 (00528424)

Co-Investigator(Kenkyū-buntansha) 楽木 宏実  大阪大学, 大学院医学系研究科 老年・腎臓内科学, 教授 (20252679)
大石 充  鹿児島大学, 大学院 医歯学総合研究科 心臓血管・高血圧内科学, 教授 (50335345)
Project Period (FY) 2011 – 2013
Keywords酸化LDL受容体 / アンジオテンシンII受容体 / 細胞内シグナル / 動脈硬化
Research Abstract

In this study, we investigated our hypothesis that the angiotensin II type 1 receptor (AT1) is involved in the oxidized LDL (oxLDL)-induced vascular responses involved in the pathogenesis of cardiovascular disease. We found that both the lectin like oxLDL receptor (LOX-1) and AT1 are required for the ability of oxLDL to activate cell signaling and that LOX-1 and AT1 form receptor complexes on cell surface membranes. Mutations in AT1 greatly reduced the capacity of oxLDL to activate G protein and MAP kinase. In addition, oxLDL induced acute blood pressure elevations in mice and these hypertensive effects were totally abolished by deletion of AT1a or LOX-1. In addition, oxLDL-induced impairment of endothelial-dependent vascular relaxation was abolished by ARB or genetic deletion of AT1 in mice. These findings indicate that oxLDL-induced activation of AT1 constitutes a heretofore unrecognized mechanism that could further contribute to the effects of oxLDL on risk for atherosclerosis.

  • Research Products

    (1 results)

All 2013

All Presentation (1 results)

  • [Presentation] シンポジウムアンジオテンシンII非依存性アンジオテンシンII受容体活性化による新たな高血圧合併症進展機構2013

    • Organizer
      第21回日本血管生物医学会
    • Year and Date
      20130000

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Published: 2015-07-16  

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