The regulation of local corticosteroid synthesis and its pathophysiological effect in the heart.

• Project/Area Number: 23790881
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Jikei University School of Medicine
• Principal Investigator: NAGOSHI Tomohisa 東京慈恵会医科大学, 医学部, 助教 (60408432)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アルドステロン / グルコース / インスリンシグナル / 心筋細胞 / Akt / ミネラロコルチコイド受容体

Research Abstract

Aldosterone plays a pivotal role in the pathogenesis of heart failure. We herein investigated the regulation of the local aldosterone synthesis and its pathophysiological effects in the heart. We demonstrated that high glucose conditions promote the expression of aldosterone synthase in cardiomyocytes. Moreover, a short-term aldosterone stimulation is found to be cardioprotective through the acute activation of insulin signaling in a mineralocorticoid receptor-independent manner. These results provide new insight into the previously unknown role of aldosterone, as a compensatory mechanism under the pathological conditions, such as heart failure, where glucose becomes an important preferential substrate for metabolism and ATP generation.

Research Products

• [Journal Article] Transient decrease in serum potassium level during ischemic attack of acute coronary syndrome: paradoxical contribution of plasma glucose level and glycohemoglobin. (2013)
  • Author(s): Sekiyama H, Nagoshi T, Komukai K, Matsushima M, Katoh D, Ogawa K, Minai K,Ogawa T, Yoshimura M.
  • Journal Title: Cardiovasc Diabetol Volume: 4 Issue: 1 Pages: 4-4
  • DOI: 10.1186/1475-2840-12-4
  • Peer Reviewed
• [Journal Article] ミネラルコルチコイド受容体拮抗薬 (2013)
  • Author(s): 名越智古、吉村道博
  • Journal Title: Nihon Rinsho Volume: 71 Pages: 594-597
  • NAID: 10031123921
• [Journal Article] RAASの新たな展開 (2013)
  • Author(s): 吉野拓哉、名越智古、吉村道博
  • Journal Title: 循環器専門医 Volume: 21 Pages: 9-15
• [Journal Article] Biphasic action of aldosterone on Akt signaling in cardiomyocytes. (2012)
  • Author(s): Nagoshi T, Date T, Fujisaki M, Yoshino T, Sekiyama H, Ogawa K, Kayama Y, Minai K, Komukai K, Ogawa T, Yoshimura M.
  • Journal Title: Horm Metab Res. Volume: 44(13) Issue: 13 Pages: 931-7
  • DOI: 10.1055/s-0032-1316343
  • Peer Reviewed
• [Journal Article] The pathophysiological role of mineralocorticoid receptor in heart failure. (2012)
  • Author(s): Nagoshi Tand Yoshimura M
  • Journal Title: Jpn J Clin Pharm Therap Volume: 43(5) Pages: 317-322
  • NAID: 10031123921
• [Journal Article] Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function. (2012)
  • Author(s): Minai K, Komukai K, Arase S, Nagoshi T, Matsuo S, Ogawa K, Kayama Y, Inada K, Tanigawa SI, Takemoto T, Sekiyama H, Date T, Ogawa T, Taniguchi I,Yoshimura M
  • Journal Title: Heart Vessels Volume: (in press)
  • Peer Reviewed
• [Journal Article] The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice. (2012)
  • Author(s): Anzawa R, Seki S, Nagoshi T, Taniguchi I, Feuvray D, Yoshimura M.
  • Journal Title: Cardiovasc Diabetol. Volume: 11 Issue: 1 Pages: 33-33
  • DOI: 10.1186/1475-2840-11-33
  • Peer Reviewed
• [Journal Article] Contribution of extracardiac factors to the inconsistency between plasma b-type natriuretic peptide levels and the severity of pulmonary congestion on chest x-rays in the diagnosis of heart failure. (2012)
  • Author(s): Nakane T, Kawai M, Komukai K, Kayama Y, Matsuo S, Nagoshi T,Minai K, Date T, Ogawa T, Yagi H, Yoshimura M
  • Journal Title: Intern. Med Volume: 51 Pages: 239-248
  • NAID: 130002061975
  • Peer Reviewed
• [Journal Article] Impact of body mass index on clinical outcome in patients hospitalized with congestive heart failure. (2012)
  • Author(s): Komukai K, Minai K, Arase S, Ogawa T, Nakane T, Nagoshi T, Kayama Y, Abe Y, Morimoto S, Ogawa K, Fujii S, Sekiyama H, Date T, Kawai M, Hongo K, Taniguchi I, Yoshimura M
  • Journal Title: Circ J. Volume: 76 Pages: 145-151
  • NAID: 10030034473
  • Peer Reviewed
• [Journal Article] カリウム保持性利尿薬・選択的アルドステロン拮抗薬 (2012)
  • Author(s): 名越智古、吉村道博
  • Journal Title: Medicina Volume: 49 Pages: 80-81
• [Journal Article] 心不全のエネルギー代謝: 糖代謝を中心に (2012)
  • Author(s): 名越智古、吉村道博
  • Journal Title: Circulation Up-to-Date Volume: 7 Pages: 36-41
• [Journal Article] 糖尿病と心不全 (2012)
  • Author(s): 名越智古、吉村道博
  • Journal Title: Anti-aging Science Volume: 4 Pages: 10-15
• [Journal Article] Contribution of extracardiac factors to the inconsistency between plasma b-type natriuretic peptide levels and the severity of pulmonary congestion on chest x-rays in the diagnosis of heart failure. (2012)
  • Author(s): Nakane T, Kawai M, Komukai K, Kayama Y, Matsuo S, Nagoshi T, Minai K, Date T, Ogawa T, Yagi H, Yoshimura M
  • Journal Title: Internal Medicine Volume: 51 Pages: 239-248
  • NAID: 130002061975
  • Peer Reviewed
• [Journal Article] Impact of body mass index on clinical outcome in patients hospitalized with congestive heart failure. (2012)
  • Author(s): Komukai K, Minai K, Arase S, Ogawa T, Nakane T, Nagoshi T, Kayama Y, Abe Y, Morimoto S, Ogawa K, Fujii S, Sekiyama H, Date T, Kawai M, Hongo K, Taniguchi I, Yoshimura M.
  • Journal Title: Circulation Journal Volume: 76 Pages: 145-151
  • NAID: 10030034473
  • Peer Reviewed
• [Journal Article] The pathophysiological role of mineralocorticoid receptor in heart failure. (2012)
  • Author(s): Nagoshi T and Yoshimura M.
  • Journal Title: Japanese Journal of Clinical Pharmacology and Therapeutics Volume: 43 Pages: 317-322
  • NAID: 10031123921
• [Journal Article] Optimization of Cardiac Metabolism in Heart Failure (2011)
  • Author(s): Nagoshi T*, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S
  • Journal Title: Curr. Pharm. Des Volume: 17 Pages: 3846-3853
  • Peer Reviewed
• [Journal Article] Impact of chronic kidney disease on the severity of initially diagnosed coronary artery disease and the patient prognosis in the Japanese population (2011)
  • Author(s): Yagi H, Kawai M, Komukai K, Ogawa T, Minai K, Nagoshi T, Ogawa K, Sekiyama H, Taniguchi I, Yoshimura M
  • Journal Title: Heart Vessels Volume: 26(4) Pages: 370-8
  • Peer Reviewed
• [Journal Article] Optimization of cardiac metabolism in heart failure. (2011)
  • Author(s): Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S.
  • Journal Title: Curr. Pharm. Des Volume: 17 Pages: 3846-3853
  • Peer Reviewed
• [Journal Article] EMPHASIS-HF試験 (2011)
  • Author(s): 名越智古、吉村道博
  • Journal Title: Cardiac Practice Volume: 22 Pages: 69-71
• [Journal Article] 心不全と抗アルドステロン薬. (2011)
  • Author(s): 名越智古、吉村道博
  • Journal Title: Circulation Up-to-Date Volume: 6 Pages: 62-69
• [Presentation] Cardio-adrenal Interaction: Cross-talk of Aldosterone Cascade with Akt Signaling in Cardiomyocytes. (2013)
  • Author(s): Nagoshi T, Yoshino T, Date T, Yoshimura M.
  • Organizer: Japanese Circulation Society 2013 Plenary Session6-3 (PL06-5)
  • Place of Presentation: Yokohama
  • Year and Date: 2013-03-17
• [Presentation] Cardio-adrenal Interaction: Cross-talk of Aldosterone Cascade with Akt Signaling in Cardiomyocytes. (2013)
  • Author(s): Nagoshi T, Yoshino T, Date T, Yoshimura M.
  • Organizer: Plenary Session, 日本循環器学会総会
  • Place of Presentation: 横浜
• [Presentation] Rapid Induction of Aldosterone Synthesis in Cultured Neonatal Rat Cardiomyocytes under High Glucose Conditions (2013)
  • Author(s): Nagoshi T, Fujisaki M, Nishikawa T, Yoshimura M.
  • Organizer: BCVS, American Heart Association
  • Place of Presentation: Las Vegas, U.S.A.
• [Presentation] Temporal and Protective Effects of Aldosterone Throught a Mineralocorticoid Receptorindependent Akt Signaling Activatin in the Heart (2012)
  • Author(s): Yoshino T, Nagoshi T,Anzawa R, Katoh D, Fujisaki M, Kayama Y, Date T, Yoshimura M
  • Organizer: Circulation2012;Abstract 12195, American Heart Assosication
  • Place of Presentation: Los Angeles
  • Year and Date: 2012-11-06
• [Presentation] Temporal and Protective Effects of Aldosterone Throught a Mineralocorticoid Receptorindependent Akt Signaling Activatin in the Heart. (2012)
  • Author(s): Yoshino T, Nagoshi T, Anzawa R, Katoh D, Fujisaki M, Kayama Y, Date T, Yoshimura M.
  • Organizer: American Heart Association
  • Place of Presentation: Los Angeles, U.S.A.
• [Presentation] Biphasic Character of Aldosterone in Cardiomyocytes Through the Akt Signaling Activation. (2011)
  • Author(s): Nagoshi T, Date T, Fujisaki M, Yoshino T, Sekiyama H, Ogawa K, Minai K, Komukai K, Ogawa T, Yoshimura M
  • Organizer: Circulation2011;124: Abstract 11268, American Heart Assosication
  • Place of Presentation: Orlando
  • Year and Date: 2011-11-14
• [Presentation] Novel, Nongenomic, and Protective Cascade of Aldosterone via Na+/H+ exchanger 1, PI3-kinase, and Akt Signaling in Cardiomyocytes. (2011)
  • Author(s): Nagoshi T,Date T, Yoshimura M
  • Organizer: Japanese Circulation Society 2011 Symposium 11-5 (SY11-5)
  • Place of Presentation: Yokohama
  • Year and Date: 2011-08-04
• [Presentation] Nongenomic, and Protective Cascade of Aldosterone via Na+/H+ exchanger 1, PI3-kinase, and Akt Signaling in Cardiomyocytes (2011)
  • Author(s): Tomohisa Nagoshi
  • Organizer: Symposium, Japanese Circulation Society(招待講演)
  • Place of Presentation: 横浜
• [Presentation] Biphasic Character of Aldosterone in Cardiomyocytes Through the Akt Signaling Activation. (2011)
  • Author(s): Tomohisa Nagoshi
  • Organizer: American Heart Assosication
  • Place of Presentation: Orlando, Florida, USA
• [Book] アルドステロンの心血管・代謝作用. 内分泌性高血圧 (最新医学別冊) (2012)
  • Author(s): 加藤大介、名越智古、吉村道博
  • Publisher: 最新医学社
• [Book] 抗アルドステロン薬. 心不全の病態と薬の使い方 (2011)
  • Author(s): 名越智古
  • Publisher: 中外医学社
• [Book] 心臓アルドステロン合成系 (2011)
  • Author(s): 名越智古、吉村道博
  • Total Pages: 3
  • Publisher: 診断と治療社