Cellular mechanism of cardio-adrenal interaction

• Project/Area Number: 25670396
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: SANO Motoaki 慶應義塾大学, 医学部, 准教授 (30265798)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 循環器・高血圧 / 細胞・組織 / 分析科学 / 心不全 / 副腎 / レニン・アンジオテンシン系 / 虚血 / アルドステロン

Research Abstract

Chronic salt overload in Dahl-salt sensitive rats stimulates aldosterone production via local activation of renin-angiotensin system (RAS). Beta3-adrenergic receptor was highly upregulated concomitant with the progression of cardio-renal injury. Adrenal glands became hypoxic as cardio-renal injury progress and both hypoxia induced the expression of beta3-adrenergic receptor via HIF activation in adrenocortical cells. Macrophages were infiltrated in the adrenal cortex in rats with cardio-renal injury and macrophage ablation reduced aldosterone production. Co-culture with macrophages or a supernatant of macrophages stimulated CYP11B2 expression in adrenocortical cells. Acquisition of catecholamine-responsiveness via the induction of beta3-adrenergic receptor under tissue ischemic and crosstalk between macrophages and adrenocortical cells accounts for the RAS-independent aldosterone production associated with cardio-renal injury.

Research Products

• [Presentation] The Unexpected Mechanism of Aldosterone Production in Salt-sensitive Dahl rats with Heart Failure (2013)
  • Author(s): Kentaro Ito, Fumiko Mitani, Shintaro Morizane, Tomohiro Matsuhashi, Yoshinori Katsumata, Xiaoxiang Yan, Tsunehisa Yamamoto, Nobuhito Goda, Keiichi Fukuda, Motoaki Sano
  • Organizer: ISHR
  • Place of Presentation: San Diego, USA (La Valencia Hotel)
  • Year and Date: 2013-06-29
• [Presentation] Emergence of β3-adrenergic Receptor and Macrophage Infiltration in the Adrenal Glands Contributed to the Unfavorable Aldosterone Production in Heart Failure (2013)
  • Author(s): Kentaro Ito, Fumiko Mitani, Shintaro Morizane , Tomohiro Matsuhashi, Yoshinori Katsumata, Xiaoxiang Yan, Tsunehisa Yamamoto, Nobuhito Goda, Keiichi Fukuda, Motoaki Sano
  • Organizer: The 6th IAFJ Award Finalists' Oral Presentation 5th International Aldosterone Forum Japan
  • Place of Presentation: Tokyo
  • Year and Date: 2013-04-21
• [Presentation] The Unexpected Mechanism of Aldosterone Production in Salt-sensitive Dahl rats with Heart Failure. (2013)
  • Author(s): Kentaro Ito, Fumiko Mitani, Shintaro Morizane , Tomohiro Matsuhashi, Yoshinori Katsumata, Xiaoxiang Yan, Tsunehisa Yamamoto, Nobuhito Goda, Keiichi Fukuda, Motoaki Sano
  • Organizer: International Symposium for Aldosterone andRelated Substances in Hypertension (Poster)
  • Place of Presentation: Sendai
• [Presentation] 心不全期副腎におけるマクロファージの浸潤とアルドステロン産生異常 (2013)
  • Author(s): 伊藤健太郎
  • Organizer: 第４回Molecular Cardiovascular Conference II
  • Place of Presentation: 北海道余市郡
• [Presentation] Emergence of β3-adrenergic Receptor and Macrophage Infiltration in the Adrenal Glands Contributed to the Unfavorable Aldosterone Production in Heart Failure (2013)
  • Author(s): Kentaro Ito, Fumiko Mitani, Shintaro Morizane , Tomohiro Matsuhashi, Yoshinori Katsumata, Xiaoxiang Yan, Tsunehisa Yamamoto, Nobuhito Goda, Keiichi Fukuda, Motoaki Sano
  • Organizer: The 6th IAFJ Award Finalists’ Oral Presentation 5th International Aldosterone Forum Japan
  • Place of Presentation: 東京
• [Presentation] The Unexpected Mechanism of Aldosterone Production in Salt-sensitive Dahl rats with Heart Failure. (2013)
  • Author(s): Kentaro Ito, Fumiko Mitani, Shintaro Morizane , Tomohiro Matsuhashi, Yoshinori Katsumata, Xiaoxiang Yan, Tsunehisa Yamamoto, Nobuhito Goda, Keiichi Fukuda, Motoaki Sano.
  • Organizer: International Symposium for Aldosterone andRelated Substances in Hypertension
  • Place of Presentation: 仙台
• [Presentation] The Unexpected Mechanism of Aldosterone Production in Salt-sensitive Dahl rats with Heart Failure. (2013)
  • Author(s): Kentaro Ito, Fumiko Mitani, Shintaro Morizane , Tomohiro Matsuhashi, Yoshinori Katsumata, Xiaoxiang Yan, Tsunehisa Yamamoto, Nobuhito Goda, Keiichi Fukuda, Motoaki Sano.
  • Organizer: ISHR
  • Place of Presentation: San Diego, USA
• [Book] 心不全とアルドステロン、コルチゾ―ル CIRCULATION Up-to-Date誌、8巻4号の Current Review(Heart Failure編) (2013)
  • Author(s): 佐野元昭、松橋智弘、勝俣良紀、伊藤健太郎
  • Publisher: メディカ
• [Book] CIRCULATION Up-to-Date 誌 (2013)
  • Author(s): 佐野元昭、松橋智弘、勝俣良紀、伊藤健太郎
  • Total Pages: 7
  • Publisher: メディカ出版