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2007 Fiscal Year Final Research Report Summary

Mechanism of aldosterone-induced vascular injury: role of angiotensin II and other factors

Research Project

Project/Area Number 18590804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YOSHIMOTO Takanobu  Tokyo Medical and Dental University, Department of Clinical and Molecular Endocrinology, assistant professor (80297457)

Project Period (FY) 2006 – 2007
Keywordsaldosterone / mineralocorticoid receptor / receptor / oxidative stress / renin-angiotensin system
Research Abstract

This study revealed several new physiological aspects of the molecular mechanisms of aldosterone-induced cardiovascular injury. We have demonstrated that Aldo directly upregulates ACE in cardiovascular tissue in aldosterone-induced hypertensive rats (Aldo-rats). ACE upregulation in cardiovascular tissue is involved in the activation of local RAS in Aldo-rats, which partly contributes to oxidative stress and inflammatory changes in cardiovascular tissue of Aldo rats. We have also shown that in cultured ECs Aldo induces of NADPH-oxidase-dependent superoxide generation via mineralocorticoid receptor (MR)-mediated Rac1 activation. In cultured mesagial cell, Aldo increased ICAM-1 and CTGF expression via SGK-1 mediated NFkB activation, and CTGF, ICAM-1, and SGK-1 immunoreactivities were increased in glomerular tissue from Aldo-rats. These results suggest that MR-mediated NADPH oxidase activation in vascular cells and local RAS activation via ACE upregulation compose "vicious cycle", thereby leading to the development of Aldo-induced cardiovascular injury, and that MR-mediated SGK-1-NFkB axis is involved in the renal injury caused by Aldo.

  • Research Products

    (42 results)

All 2008 2007 2006

All Journal Article (27 results) (of which Peer Reviewed: 7 results) Presentation (14 results) Book (1 results)

  • [Journal Article] Aldosterone-stimulated SGK1 activity mediates profibrotic signaling in the mesangium2008

    • Author(s)
      Terada Y, Kuwana H, et al.
    • Journal Title

      J Am Soc Nephrol 19

      Pages: 298-309

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Aldosterone induces superoxide generation via Rac1 activation in endothelial cells2008

    • Author(s)
      Iwashima F, Yoshimoto T, et al.
    • Journal Title

      Endocrinology 149

      Pages: 1009-1014

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Aldosterone-stimulated SGK1 activity mediates profibrotic signaling in the mesangium.2008

    • Author(s)
      Terada Y, Kuwana H, et al.
    • Journal Title

      J Am Soc Nephrol 19

      Pages: 298-309

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Aldosterone induces superoxide generation via Racl activation in endothelial cells.2008

    • Author(s)
      Iwashima F, Yoshimoto T, et al.
    • Journal Title

      Endocrinology 149

      Pages: 1009-1014

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Angiotensin II receptor type 1- mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension : the possible role of local renin-angiotensin system2007

    • Author(s)
      Hirono Y, Yoshimoto T, et al.
    • Journal Title

      Endocrinology 148

      Pages: 1688-1696

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Systemic distribution of salusin expression in the rats2007

    • Author(s)
      Suzuki N, Shichiri M, et al.
    • Journal Title

      Hypertens Res 30

      Pages: 1255-1262

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Chronic blockade of nitric oxide synthesis reduces adiposity and improves insulin resistance in high-fat-induced obese mice2007

    • Author(s)
      Tsuchiya K, Sakai H, et al.
    • Journal Title

      Endocrinology 148

      Pages: 4548-4556

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Aldosterone as a cardiovascular risk hormone2007

    • Author(s)
      Yoshimoto T, Hirata Y
    • Journal Title

      Endocrine J 54

      Pages: 359-370

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 血管内皮障害とアルドステロン2007

    • Author(s)
      吉本貴宣, 他
    • Journal Title

      医学のあゆみ 221

      Pages: 739-742

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Angiotensin II receptor type 1- mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system.2007

    • Author(s)
      Hirono Y, Yoshimoto T, et al.
    • Journal Title

      Endocrinology 148

      Pages: 1688-1696

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Systemic distribution of salusin expression in the rats.2007

    • Author(s)
      Suzuki N, Shichiri M, et al.
    • Journal Title

      Hypertens Res 30

      Pages: 1255-1262

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chronic blockade of nitric oxide synthesis reduces adiposity and improves insulin resistance in high-fat-induced obese mice.2007

    • Author(s)
      Tsuchiya K, Sakai H, et al.
    • Journal Title

      Endocrinology 148

      Pages: 4548-4556

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Aldosterone as a cardiovascular risk hormone.2007

    • Author(s)
      Yoshimoto T, Hirata Y.
    • Journal Title

      Endocrine J 54

      Pages: 359-370

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Endothelial injury and aldosterone.2007

    • Author(s)
      Yoshimoto T, Hirata Y.
    • Journal Title

      Igaku no Ayumi 221

      Pages: 739-742

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Caridiovascular function of aldosterone2007

    • Author(s)
      Yoshimoto T
    • Journal Title

      Genpatsusei Aldosterone-shou Shinryou Manual (Shindan-To-Chiryou Sha) Tokyo

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Angiotensin II induces monocyte chemoattractant protein-1 expression via nuclear factor-kappa B-dependent pathway in rat preadipocytes2006

    • Author(s)
      Tsuchiya K, Yoshimoto T, et al.
    • Journal Title

      Am J Physiol Endocrinol Metab 291

      Pages: E771-E778

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 心血管障害におけるアルドステロンの病態生理学的意義2006

    • Author(s)
      吉本貴宣, 他
    • Journal Title

      血管 29

      Pages: 47-55

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] アルドステロンによる血管作用2006

    • Author(s)
      吉本貴宣, 他
    • Journal Title

      血圧 13

      Pages: 721-725

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 心血管リスクホルモンとしてのアルドステロン2006

    • Author(s)
      吉本貴宣, 他
    • Journal Title

      細胞 38

      Pages: 16-19

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] アルドステロン誘導性血管炎の発症機構2006

    • Author(s)
      吉本貴宣, 他
    • Journal Title

      内分泌・糖尿病科 23

      Pages: 587-592

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 「アルドステロン誘導性血管炎」発症の分子機構2006

    • Author(s)
      廣野由紀, 他
    • Journal Title

      血管 29

      Pages: 139-144

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Angiotensin II induces monocyte chemoattractant protein-1 expression via nuclear factor-kappa B-dependent pathway in rat preadipocytes.2006

    • Author(s)
      Tsuchiya K, Yoshimoto T, et al.
    • Journal Title

      Am J Physiol Endocrinol and Metab 291

      Pages: E771-778

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pathophysiological significance of aldosterone in cardiovascular disease.2006

    • Author(s)
      Yoshimoto T, Hirata Y.
    • Journal Title

      Kekkan 29

      Pages: 47-55

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vascular effect by aldosterone2006

    • Author(s)
      Yoshimoto T, Hirata Y.
    • Journal Title

      Ketsuatsu 13

      Pages: 721-725

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Aldosterone as a cardiovascular risk hormone2006

    • Author(s)
      Yoshimoto T, Hirata Y.
    • Journal Title

      Saibou 38

      Pages: 16-19

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pathogenesis of aldosterone-induced vasculitis2006

    • Author(s)
      Yoshimoto T, Hirata Y.
    • Journal Title

      Naibunpitsu Tounyoubyou-Ka 23

      Pages: 587-592

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular mechanisms of aldosterone-inducecdvas2006

    • Author(s)
      Hirono Y, Yoshimoto T, et al.
    • Journal Title

      Kekkan 29

      Pages: 139-144

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] アルドステロンによるミネラロコルチコイド受容体(MR)を介した血管障害のメカニズム2007

    • Author(s)
      吉本貴宣, 他
    • Organizer
      第11回日本心血管内分泌代謝学会学術総会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] アルドステロンによるRac1活性化を介した血管内皮細胞での活性酸素産生2007

    • Author(s)
      岩嶋富美子, 他
    • Organizer
      第11回日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Mechanisms of aldosterone-induced vascular injury through mineralocorticoid receptor.2007

    • Author(s)
      Yoshimoto T, et al.
    • Organizer
      10^<th> Nihon Shin-kekkann Naibunpitsu Taisha Gakkai Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Aldosterone-induced ROS genereation in endothelium2007

    • Author(s)
      Iwashima P, et al.
    • Organizer
      10^<th> Nihon Shin-kekkann Naibunpitsu Gakkai
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Possible involvement of small GTP-binding protein, Rac-1, in aldosterone-stimulated superoxide production in endothelial cells2007

    • Author(s)
      Iwashima F, et al.
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      Tronto
    • Year and Date
      2007-06-03
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Possible involvement of small GTP-binding protein, Rac-1, in aldosterone-stimulated superoxideproduction in endothelial cells2007

    • Author(s)
      Iwashima F, et al.
    • Organizer
      The Endocrine Society Annual Meeting
    • Place of Presentation
      Tronto
    • Year and Date
      2007-06-03
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] アルドステロン負荷高血圧モデルラットにおいて選択的ホスホジエステラーゼ3阻害薬シロスタゾールはールは心血管保護作用を示す2007

    • Author(s)
      櫻田麻耶, 他
    • Organizer
      第36回日本心脈管作動物質学会
    • Place of Presentation
      徳島
    • Year and Date
      2007-02-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Cilostasol showed cardiovascular protection in Aldosterone induced-hypertensive rats2007

    • Author(s)
      Sakurada M, et al.
    • Organizer
      36^<th> Nihon Shin-Myakkan Sadoubusshitsu Gakkai
    • Place of Presentation
      Tokushima
    • Year and Date
      2007-02-09
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 血管内皮細胞を主座としたアルドステロン誘導性血管炎の分子機構2006

    • Author(s)
      吉本貴宣, 他
    • Organizer
      第10回日本心血管内分泌代謝学会シンポジウム
    • Place of Presentation
      福井
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] アルドステロンによる血管内皮細胞での活性酸素産生機構2006

    • Author(s)
      岩嶋富美子, 他
    • Organizer
      第10回日本心血管内分泌代謝学会
    • Place of Presentation
      福井
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Aldosterone-induced vaculitis based on endothelial injury2006

    • Author(s)
      Yoshimoto T, et al.
    • Organizer
      10^<th> Nihon Shin-kekkann Naibunpitsu Taisha Gakkai Symposium
    • Place of Presentation
      Fukui
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ROS generation induced by aidosterone in endothelium2006

    • Author(s)
      Iwahsima F, et al.
    • Organizer
      10^<th> Nihon Shin-kekkann Naibunpitsu Taisha Gakkai
    • Place of Presentation
      Fukui
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Possible involvement of vascular renin-angiotensin system in the development of aldosterone-induced vascular injury in rats2006

    • Author(s)
      Yoshimoto T, et al.
    • Organizer
      The 21st Scientific Meeting of the international Society of Hypertension Investigator-Initiated Symposia
    • Place of Presentation
      Takarazuka
    • Year and Date
      2006-10-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Possible involvement of vascular renin-angiotensin system in the development of aldosterone-induced vascular injury in rats2006

    • Author(s)
      Yoshimoto T, et al.
    • Organizer
      The 21st Scientific Meeting of the International Society of Hypertension Investigator-Initiated Symposia: Chymase Comprehending Tissue-Angiotensin Generating System
    • Place of Presentation
      Takarazuka
    • Year and Date
      2006-10-20
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 原発性アアルドステロン症診療マニュアル2007

    • Author(s)
      吉本貴宣
    • Total Pages
      2
    • Publisher
      診断と治療社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-06-09  

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