Role of intracellular renin and (pro)renin receptor in cardiac myocytes

• Project/Area Number: 23591036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: KATOH Hideki 浜松医科大学, 医学部, 助教 (80314029)
• Co-Investigator(Kenkyū-buntansha): SATOH Hiroshi 浜松医科大学, 医学部付属病院, 講師 (30293632) ; SAOTOME Masao 浜松医科大学, 医学部付属病院, 助教 (70509512) ; HAYASHI Hideharu 浜松医科大学, 医学部, 教授 (50135258)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: レニン / 糖尿病 / ミトコンドリア / 心筋虚血 / 虚血再灌流障害 / ﾚﾆﾝ / ﾐﾄｺﾝﾄﾞﾘｱ / 組織ﾚﾆﾝ、ﾌﾟﾛﾚﾆﾝ

Research Abstract

In this study, we found that expression of intracellular renin increased both in cytosol and mitochondriaduring ischemia in diabetic heart, and that increased renin protects cardiomyocytes from ischemic injury. This protective effect of renin is due to the reduction of UCP and acceleration of electron transport chain, which resulted in the prevention of mitochondrial depolarization and preservation of ATP production under ischemic stress. The cardioprotective effect of renin is independent from subsequent intracellular angiotensin II production.
These results indicated that in contrast to previously reported adverse effects of circulating RAS, cytosolic renin plays an important role to protect myocytes from ischemic stress in diabetic heart.

Research Products

• [Journal Article] Distribution of late gadolinium enhancement in end-stage hypertrophic cardiomyopathy and dilated cardiomyopathy : Differential diagnosis and prediction of cardiac outcome (2014)
  • Author(s): Machii M, Satoh H, Shiraki K, Saotome M, Urushida T, Katoh H, Takehara Y, Sakahara H, Ohtani H, Wakabayashi Y, Ukigai H, Twarahara K, Hayashi H.
  • Journal Title: Magnetic Resonance Imaging Volume: Vol. 32
• [Journal Article] Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes (2014)
  • Author(s): Kumazawa A, Katoh H, Nonaka D, Watanabe T, Saotome M, Urushida T, Satoh H, Hayashi H.
  • Journal Title: Circ J Volume: Vol. 78
  • NAID: 130003391082
• [Journal Article] Distribution of late gadolinium enhancement in end-stage hypertrophic cardiomyopathy and dilated cardiomyopathy: differential diagnosis and prediction of cardiac outcome. (2014)
  • Author(s): Machii M, Satoh H, Shiraki K, Saotome M, Urushida T, Katoh H, Takehara Y, Sakahara H, Ohtani H, Wakabayashi Y, Ukigai H, Tawarahara K, Hayashi H.
  • Journal Title: Magn Reson Imaging. Volume: 32 Issue: 2 Pages: 118-124
  • DOI: 10.1016/j.mri.2013.10.011
  • Peer Reviewed
• [Journal Article] Microtubule disorganization affects the mitochondrial permeability transition pore in cardiac myocytes. (2014)
  • Author(s): Kumazawa A, Katoh H, Nonaka D, Watanabe T, Saotome M, Urushida T, Satoh H, Hayashi H.
  • Journal Title: Circulation Journal Volume: 78 Pages: 1026-1015
  • NAID: 130003391082
• [Journal Article] Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance. (2014)
  • Author(s): Watanabe T, Saotome M, Nobuhara M, Sakamoto A, Urushida T, Katoh H, Satoh H, Funaki M, Hayashi H.
  • Journal Title: Exp Cell Res. Volume: 323 Issue: 2 Pages: 314-325
  • DOI: 10.1016/j.yexcr.2014.02.027
  • Peer Reviewed
• [Journal Article] Mitochondrial dysfunction caused by saturated fatty acid loading induces myocardial insulin-resistance in differentiated H9c2 myocytes : a novel ex vivo myocardial insulin-resistance model (2013)
  • Author(s): Nobuhara M, Saotome M, Watanabe T, Urushida T, Katoh H, Satoh H, Funaki M, Hayashi H.
  • Journal Title: Exp Cell Res Volume: Vol. 319
• [Journal Article] Ultrasound analysis of the relationship between right internal jugular vein and common carotid artery in the left head rotation and head flexion position (2013)
  • Author(s): Saitoh T, Satoh H, Kumazawa A, Nobuhara M, Machii M, Tanaka T, Shiraki K, Saotome M, Urushida T, Katoh H, Hayashi H.
  • Journal Title: Heart Vessels Volume: Vol. 28
• [Journal Article] Pregnancy-related acute myocardial infarction in Japan: a review of epidemiology, etiology and treatment from case reports. (2013)
  • Author(s): Satoh H, Sano M, Suwa K, Saotome M, Urushida T, Katoh H, Hayashi H.
  • Journal Title: Circulation Journal Volume: 77 Issue: 7 Pages: 725-723
  • DOI: 10.1016/j.yexcr.2013.02.004
  • NAID: 10031138964
  • Peer Reviewed
• [Journal Article] Effects of nitric oxide on mitochondrial permeability transition pore and thiol-mediated responses in cardiac myocytes (2012)
  • Author(s): Ohtani H, Katoh H, Tanaka T, Saotome M, Urushida T, Satoh H, Hayashi H.
  • Journal Title: Nitric Oxide Volume: Vol. 26 Pages: 95-101
• [Journal Article] Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine (2011)
  • Author(s): Saitoh T, Satoh H, Nobuhara M, Machii M, Tanaka T, Ohtani H, Saotome M, Urushida T, Katoh H, Hayashi H.
  • Journal Title: Heart and Vessels Volume: Vol. 26
• [Presentation] Intracellular renin prevents ischemic injury by modulating mitochondrial function in diabetic heart (2013)
  • Author(s): Nonaka D, Katoh H, Kumazawa A, Saotome M, Urushida T, Satoh H, Hayashi H.
  • Organizer: American Heart Association
  • Place of Presentation: Dallas, USA
  • Year and Date: 2013-11-04
• [Presentation] Non-secretory renin prevents ischemic injury by modulating mitochondrial function in diabetic heart (2013)
  • Author(s): Nonaka D, Katoh H, Kumazawa A, Saotome M, Urushida T, Satoh H, Hayashi H.
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Amsterdam, Nederland
  • Year and Date: 2013-09-04
• [Presentation] Non-secretory renin prevents ischemic injury by modulating mitochondrial function in diabetic heart (2013)
  • Author(s): Nonaka D, Katoh H, Kumazawa A, Saotome M, Urushida T, Satoh H, Hayashi H.
  • Organizer: World congress of International Society of Heart Research
  • Place of Presentation: Sandiego USA
  • Year and Date: 2013-06-22
• [Presentation] Non-secretory renin prevents ischemic injury by modulating mitochondrial function in diabetic heart. (2013)
  • Author(s): Daishi Nonaka
  • Organizer: XXI ISHR World Congress
  • Place of Presentation: San Diego, United States
• [Presentation] Non-secretory renin prevents ischemic injury by modulating mitochondrial function in diabetic heart (2013)
  • Author(s): Daishi Nonaka
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] Intracellular renin prevents ischemic injury by modulating mitochondrial function in diabetic heart. (2013)
  • Author(s): Daishi Nonaka
  • Organizer: American Heart Association 2013 Scientific Sessions
  • Place of Presentation: Dallas, United States
• [Presentation] Microtubules are related to the regulation of mitochondrial permeability transition pore in rat cardiac myocytes (2012)
  • Author(s): Kumazawa A, Katoh H, Hayashi H.
  • Organizer: 第35回心筋代謝研究会
  • Year and Date: 2012-06-22
• [Presentation] Local Ca^<2+> Releases from the sarcoplasmic reticulum are required for microtubule-related mitochondrial dysfunction in rat ventricular myocytes (2012)
  • Author(s): Kumazawa A, Katoh H, Nonaka D, Saotome M, Urushida T , Satoh H , Hayashi H.
  • Organizer: 第76回日本循環器学会学術集会
  • Year and Date: 2012-03-21
• [Presentation] Microtubule stability is related to mitochondrial function in rat ventricular myocytes (2011)
  • Author(s): Kumazawa A, Katoh H, Nonaka D, Saotome M, Urusida T, Satoh H, Hayashi H.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 2011-11-09
• [Presentation] A novel ex vivo model to investigate metabolic deficiency in cardiac myocyres : differentiated H9C2 cells to assess the insulin-resistant heart (2011)
  • Author(s): Nobuhara M, Saotome M, Watanabe T ,Nonaka D, Kumazawa A, Machii M, Tanaka T, Shiraki K, Urushida T, Katoh H, Satoh H, Hayashi H.
  • Organizer: Annual Biophysical Meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2011-03-14