A novel strategy using radical scavengers against intermittent hypoxia-induced oxidative stress in heart, kidney, and brain

• Project/Area Number: 23590267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Osaka Medical College
• Principal Investigator: HAYASHI TETSUYA 大阪医科大学, 医学部, 非常勤講師 (30257852)
• 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: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 間歇的低酸素負荷 / 糖尿病マウス / 心筋症ハムスター / 酸化ストレス / 水素ガス / ラジカルスカベンジャー / 大脳辺縁系 / Fos / 肺高血圧症 / VEGF / β1受容体遮断薬 / 心リモデリング / ラジカル消去 / 脂質代謝異常

Research Abstract

Intermittent hypoxia (IH) relevant to sleep apnea is known to increase the risk of cardiovascular morbidity and mortality. This study showed that IH increased superoxide production, oxidative stress, and inflammatory cytokine expression in heart and kidney, accelerating histological degeneration due to hypoxic stress. Inhalation of hydrogen (H2) gas improved lipid metabolism and reduced oxidative stress. Furthermore, H2 gas improved the deteriorated systolic function in Bio14.6 cardiomyopathic hamster exposed to IH. On the other hand, treatment with celiprolol, a beta 1-selective adrenoreceptor blocker, suppressed blood pressure fluctuation during IH, restored eNOS expression, and attenuated cardiac remodeling caused by IH. Intriguingly, limbic Fos expression was significantly suppressed in obese diabetic mice exposed to IH, associated with sedative and/or depressive behavioral signs, which may related to the neuropsychological disturbances in diabetic patients with sleep apnea.

Research Products

• [Journal Article] O-Linked N-Acetyl Glucosamine (O-GlcNAc) Regulates Autophagy and Apoptosis in Cardiomyocytes: a Double-Edged Sword in Intermittent Hypoxia-Induced Cardiac Remodeling (2014)
  • Author(s): Hayashi T, Sasaki M, Watanabe A, Furukawa Y, Nakagawa T, Nomura A, Uehashi W, Kato R, Ijiri Y, Yamaguchi T, Izumi Y, Yoshiyama M, Asahi M
  • Journal Title: J Am Coll Cardiol Volume: 63
  • Peer Reviewed
• [Journal Article] Intermittent Hypoxia Accelerates Cardiac Remodeling and Systolic Dysfunction in Cardiomyopathic Hamster (2014)
  • Author(s): Nomura A, Kato R, Ijiri Y, Sakamoto A, Yamaguchi T, Izumi Y, Yoshiyama M, Tanaka K, Hayashi T
  • Journal Title: Circulation Journal Volume: 78 Pages: 1913-1913
  • Peer Reviewed
• [Journal Article] Celiprolol reduces oxidative stress and attenuates left ventricular remodelingiInduced by hypoxic stress in mice (2013)
  • Author(s): Nishioka S, Yoshioka T, Nomura A, Kato R, Miyamura M, Okada Y, Ishizaka N, Matsumura Y, Hayashi T
  • Journal Title: Hypertension Research Volume: 36 Issue: 11 Pages: 934-939
  • DOI: 10.1038/hr.2013.60
  • Peer Reviewed
• [Journal Article] Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice (2013)
  • Author(s): Mukai T, Nagao Y, Nishioka S, Hayashi T, Shimizu S, Ono A, Sakagami Y, Watanabe S, Ueda Y, Hara M, Tokudome K, Kato R, Matsumura Y, Ohno Y
  • Journal Title: Neuroscience Res Volume: 77 Issue: 4 Pages: 202-207
  • DOI: 10.1016/j.neures.2013.09.013
• [Journal Article] Celiprolol reduces oxidative stress and attenuates left ventricular remodelingiInduced by hypoxic stress in mice. (2013)
  • Author(s): Nishioka S, Yoshioka T, Nomura A, Kato R, Miyamura M, Okada Y, Ishizaka N, Matsumura Y, Hayashi T.
  • Journal Title: Hypertens Res Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats. (2012)
  • Author(s): Kato R, Higashitani A, Irie T, Kusukawa Y, Yamamoto Y, Nakagawa M, Urashima Y, Nagata M, Hayashi T, Ijiri Y, Tanaka K.
  • Journal Title: Xenobiotica Volume: 242 Pages: 798-807
  • Peer Reviewed
• [Journal Article] Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice (2011)
  • Author(s): Hayashi T, Yoshioka T, Hasegawa K, Miyamura M, Mori T, Ukimura A, Matsumura Y, Ishizaka N
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 301 Issue: 3 Pages: 1062-1069
  • DOI: 10.1152/ajpheart.00150.2011
  • Peer Reviewed
• [Presentation] O-Linked N-Acetyl Glucosamine (O-GlcNAc) Regulates Autophagy and Apoptosis in Cardiomyocytes : a Double-Edged Sword in Intermittent Hypoxia-Induced Cardiac Remodeling (2014)
  • Author(s): Hayashi T, Sasaki M, Watanabe A, Furukawa Y, Nakagawa T, Nomura A, Uehashi W, Kato R, Ijiri Y, Yamaguchi T, Izumi Y, Yoshiyama M, Asahi M
  • Organizer: 64th ACC Congress 2014
  • Place of Presentation: Washington DC, USA
• [Presentation] Intermittent hypoxia accelerates cardiac remodeling and systolic dysfunction in cardiomyopathic hamster (2014)
  • Author(s): Nomura A, Kato R, Ijiri Y, Sakamoto A, Yamaguchi T, Izumi Y, Yoshiyama M, Tanaka K, Hayashi T
  • Organizer: 第78回日本循環器学会総会
  • Place of Presentation: 東京
• [Presentation] O-Linked N-Acetyl Glucosamine (O-GlcNAc) Regulates Autophagy and Apoptosis in Cardiomyocytes: a Double-Edged Sword in Intermittent Hypoxia-Induced Cardiac Remodeling (2014)
  • Author(s): Hayashi T, Sasaki M, Watanabe A, Furukawa Y, Nakagawa T, Nomura A, Uehashi W, Kato R, Ijiri Y, Yamaguchi T, Izumi Y, Yoshiyama M, Asahi M
  • Organizer: 64th ACC Congress 2014
  • Place of Presentation: Washington DC, USA
• [Presentation] Role of Vascular Endothelial Growth Factor in Cardiac Remodeling due to Hypoxic Stress (2013)
  • Author(s): Woo E, Nishioka S, NemotoS, Katsumata T, Hayashi T
  • Organizer: 23rd European Meeting on Hypertension & Cardiovascular Protection
  • Place of Presentation: Milan, Italy
• [Presentation] 間歇的低酸素曝露による左室リモデリングに対する新規ARB azilsartanの効果 (2013)
  • Author(s): 上橋和佳, 野村篤生, 加藤隆児, 宮村昌利, 井尻好雄, 石坂信和, 林哲也
  • Organizer: 第61回日本心臓病学会
  • Place of Presentation: 熊本
• [Presentation] 間歇的低酸素負荷が不全心に及ぼす影響と水素ガスのラジカルスカベンジ効果 (2013)
  • Author(s): 供田菜々花, 野村篤生, 加藤隆児, 井尻好雄, 宮村昌利, 石坂信和, 阪本英二, 田中一彦, 林哲也
  • Organizer: 第61回日本心臓病学会
  • Place of Presentation: 熊本
• [Presentation] 間歇的低酸素負荷に伴う血圧変動と酸化ストレスに対するceliprololの有効性 (2013)
  • Author(s): 東森健志, 西岡慧, 野村篤生, 加藤隆児, 宮村昌利, 石坂信和, 松村靖夫, 林哲也
  • Organizer: 第36回日本高血圧学会総会
  • Place of Presentation: 大阪
• [Presentation] Azilsartan reduces oxidative stress and attenuates cardiac remodeling induced by hypoxia in rats (2013)
  • Author(s): Fujiwara Y, Nomura A, Kato R, Miyamura M, Ijiri Y, Ishizama N, Hayashi T
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 大宮
• [Presentation] Effect of hydrogen gas inhalation on lipid metabolism and left ventricular remodeling induced by intermittent hypoxia (2012)
  • Author(s): Nishioka S, Hayashi T, Miyamura M, Mori T, Ukimura A, Okada Y, Ishizaka N, Yoshioka T, Hasegawa K, Matsumura
  • Organizer: ESC Congress 2012
  • Place of Presentation: Munich
• [Presentation] Intermittent hypoxia- induced cardiovascular remodeling in diabetes mellitus (2012)
  • Author(s): Nomura A, Nishioka S, Yamaguchi S, Tagawa A, Furukawa Y, Kato R, Ijiri Y, Matsumura Y, Okada Y, Asahi M, Tanaka K, Hayashi T
  • Organizer: 第35回心筋代謝研究会
  • Place of Presentation: 東京
• [Presentation] 持続的低酸素曝露にともなう心室リモデリングにおけるVEGFの意義と重要性 (2012)
  • Author(s): 禹英喜, 根本慎太郎, 勝間田敬弘, 松村靖夫, 林哲也
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
• [Presentation] Effect of hydrogen gas inhalation on lipid metabolism and left ventricular remodeling induced by intermittent hypoxia. (2012)
  • Author(s): Nishioka S, Hayashi T, Miyamura M, Mori T, Ukimura A, Okada Y, Ishizaka N, Yoshioka T, Hasegawa K, Matsumura.
  • Organizer: ESC Congress 2012
  • Place of Presentation: Munich
• [Presentation] Intermittent hypoxia-induced cardiovascular remodeling in diabetes mellitus. (2012)
  • Author(s): Nomura A, Nishioka S, Yamaguchi S, Tagawa A, Furukawa Y, Kato R, Ijiri Y, Matsumura Y, Okada Y, Asahi M, Tanaka K, Hayashi T.
  • Organizer: 第35回心筋代謝研究会
  • Place of Presentation: 東京
• [Presentation] 持続的低酸素曝露にともなう心室リモデリングにおけるVEGFの意義と重要性. (2012)
  • Author(s): 禹英喜、根本慎太郎、勝間田敬弘、松村靖夫、林哲也.
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
• [Presentation] Inhalation of hydrogen gas reduces oxidative stress and attenuates cardiac remodeling induced by intermittent hypoxia in mice. (2011)
  • Author(s): Hayashi T.
  • Organizer: 21st European Meeting on Hypertension
  • Place of Presentation: Milan
• [Presentation] Efficacy of anti-oxidative beta-blocker on intermittent hypoxia-induced left ventricular remodeling in mice.
  • Author(s): Miyamura M, Hayashi T.
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] 間歇的低酸素負荷にともなう左室リモデリングに対する水素ガス吸入の効果.
  • Author(s): 林哲也
  • Organizer: 第43回日本臨床分子形態学会総会・学術集会
  • Place of Presentation: 高槻
• [Presentation] 間歇的低酸素曝露によって惹起される左室リモデリングに対するβ-受容体遮断薬の効果.
  • Author(s): 宮村昌利、林哲也
  • Organizer: 第59回日本心臓病学会学術集会
  • Place of Presentation: 神戸
• [Remarks] 大阪薬科大学循環病態治療学研究室
  • URL: http://www.oups.ac.jp/kenkyu/kenkyuushitu/jyunkanbyoutaitiryo.html
• [Remarks] 大阪薬科大学ホームページ循環病態治療学研究室
  • URL: http://www.oups.ac.jp/kenkyu/kenkyuushitu/jyunkanbyoutaitiryo.html