Study for cardioprotection of omega-3 polyunsaturated fatty acid

• Project/Area Number: 26461065
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Sato Hiroshi 浜松医科大学, 医学部附属病院, 講師 (30293632)
• Co-Investigator(Kenkyū-buntansha): 漆田 毅 浜松医科大学, 医学部, 助教 (20334980) ; 林 秀晴 浜松医科大学, 医学部, 教授 (50135258) ; 早乙女 雅夫 浜松医科大学, 医学部附属病院, 助教 (70509512) ; 加藤 秀樹 浜松医科大学, 医学部, 助教 (80314029)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 不飽和脂肪酸 / 心筋細胞 / 冠動脈疾患 / ミトコンドリア / 培養心筋細胞 / 飽和脂肪酸 / ω-3不飽和脂肪酸 / 膜電位 / 細分化

Outline of Final Research Achievements

(Basic study) When differentiated H9c2 myocytes were exposed to palmitate (PAL), the myocytes showed activation of caspases 3/7, depolarization of mitochondrial membrane potential, depletion of intracellular ATP, and enhancement of reactive oxygen species production. PAL enhanced mitochondrial fragmentation with increased dynamin-related protein-1 (Drp1) expression. Eicosapentaenoic acid (EPA) ameliorated the PAL-induced lipotoxicity via AMP-activated protein kinase activation, which suppressed mitochondrial fragmentation and Drp1 expression. (Clinical study) Patients with fish intake >=3 times/week showed higher EPA, DHA levels and EPA/AA ratio than those with <3 times/week. Both patients recommended fish intake and those treated with EPA showed decreases in serum MDA-LDLlevels after 2 years, but the extent did not differ. The increase in fish intake was as effective as the treatment with EPA for increases in serum omega-3 polyunsaturated fatty acids and a decrease in oxidative LDL.

Research Products

• [Journal Article] Eicosapentaenoic acid ameliorates palmitate-induced lipotoxicity via the AMP kinase/dynamin-related protein-1 signaling pathway in differentiated H9c2 myocytes. (2017)
  • Author(s): Sakamoto A, Saotome M, Hasan P, Satoh T, Ohtani H, Urushida T, Katoh H, Satoh H, Hayashi H
  • Journal Title: Exp Cell Res Volume: 351 Issue: 1 Pages: 109-120
  • DOI: 10.1016/j.yexcr.2017.01.004
  • Peer Reviewed
• [Journal Article] Characterizing saccular aortic arch aneurysms from the geometry-flow dynamics relationship (2016)
  • Author(s): Natsume K, Shiiya N, Takehara Y, Sugiyama M, Satoh H, Yamashita K, Washiyama N
  • Journal Title: J Thorac Cardiovasc Surg Volume: 16 Issue: 6 Pages: 31626-31629
  • DOI: 10.1016/j.jtcvs.2016.11.032
  • Peer Reviewed
• [Journal Article] Late gadolinium enhancement and therisk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: Systematic review and meta-analysis. (2016)
  • Author(s): Di Marco A, Anguera I, Schmitt M, Klem I, Neilan T, White JA, Sramko M, Masci PG, Barison A, Mckenna P, Mordi I, Haugaa KH, Leyva F, Rodriguez Capit&aacute;n J, Satoh H, Nabeta T, Dallaglio PD, Campbell NG, Sabat&eacute; X, Cequier &Aacute;
  • Journal Title: JACC Heart Fail Volume: - Issue: 1 Pages: 28-38
  • DOI: 10.1016/j.jchf.2016.09.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intra-left ventricular flow dynamics in patients with preserved and impaired left ventricular function: analysis with three-dimensional cine phase contrast magnetic resonance imaging (4D-Flow). (2016)
  • Author(s): Suwa K, Saitoh T, Takehara Y, Sano M, Saotome M, Urushida T, Katoh H, Satoh H, Sugiyama M, Wakayama T, Alley M, Sakahara H, Hayashi H
  • Journal Title: J Magn Reson Imaging Volume: 44 Issue: 6 Pages: 1493-1503
  • DOI: 10.1002/jmri.25315
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intra-cardiac distribution of late gadolinium enhancement in cardiac sarcoidosis and dilated cardiomyopathy. (2016)
  • Author(s): Sano M, Satoh H, Suwa K, Saotome M, Urushida T, Katoh H, Hayashi H, Saitoh T.
  • Journal Title: World J Cardiol Volume: 8 Issue: 9 Pages: 496-503
  • DOI: 10.4330/wjc.v8.i9.496
  • Peer Reviewed
• [Journal Article] 妊娠関連の急性心筋梗塞に対する集学的管理の重要性。 (2016)
  • Author(s): 佐藤 洋, 佐野 誠, 林 秀晴
  • Journal Title: 循環器専門医「特集II：第79回日本循環器学会学術集会」心疾患の妊娠と出産―チーム管理の重要性 Volume: 1 Pages: 21-26
  • NAID: 130006575722
• [Journal Article] Aberrant serum polyunsaturated fatty acids profile is relevant with acute coronary syndrome. (2016)
  • Author(s): Sakamoto A, Saotome M, Hosoya N, Kageyama S, Yoshizaki T, Takeuchi R, Murata K, Nawada R, Onodera T, Takizawa A, Satoh H, Hayashi H
  • Journal Title: Heart and Vessels Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] MRI and the exercise blood pressure response in dilated cardiomyopathy. (2015)
  • Author(s): Satoh H
  • Journal Title: Heart Volume: １０１ Issue: 10 Pages: 747-748
  • DOI: 10.1136/heartjnl-2014-307426
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of Intra-Left Atrial Flow Dynamics and Factors Affecting Formation of the Vortex Flow (2014)
  • Author(s): Suwa K, Saitoh T, Takehara Y, Sano M, Nobuhara M, Saotome M, Urushida T, Katoh H, Satoh H, Sugiyama M, Wakayama T, Sakahara H, Hayashi H.
  • Journal Title: Circulation Journal Volume: 79 Issue: 1 Pages: 144-152
  • DOI: 10.1253/circj.CJ-14-0562
  • NAID: 130004704021
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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: 1206-1215
  • NAID: 130003391082
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional, morphological and electrocardiographical abnormalities in patients with apical hypertrophic cardiomyopathy and apical aneurysm: correlation with cardiac MR. (2014)
  • Author(s): Suwa K, Satoh H, Sano M, Nobuhara M, Saitoh T, Saotome M, Urushida T, Katoh H, Tawarahara K, Ohtani H, Wakabayashi Y, Takase H, Terada H, Takehara Y, Sakahara H, Hayashi H
  • Journal Title: Ｏｐｅｎ Ｈｅａｒｔ Volume: １ Issue: 1 Pages: e000124-e000124
  • DOI: 10.1136/openhrt-2014-000124
  • Peer Reviewed / Open Access
• [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] 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] Distribution of late gadolinium enhancement in various types of cardiomyopathies: Significance in differential diagnosis, clinical features and prognosis. (2014)
  • Author(s): Satoh H, Sano M, Suwa K, Saitoh T, Nobuhara M, Saotome M, Urushida T, Katoh H, Hayashi H
  • Journal Title: World J Cardiol. Volume: ６ Issue: 7 Pages: 585-601
  • DOI: 10.4330/wjc.v6.i7.585
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial remodeling in coronary heart disease. (2014)
  • Author(s): Saotome M, Hajnóczky G, Katoh H, Satoh H, Hayashi H
  • Journal Title: Research Reports in Clinical Cardiology Volume: ５ Pages: 111-122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] A Multidimensional Approach Using a Dual Biomarker Method and Cardiac Imaging for the Screening of Fabry Disease with Cardiac Involvement (2017)
  • Author(s): Yamashita S, Satoh H, Hayashi H, urushida T, Saotome M , Ohtani H..
  • Organizer: The 81th Annual Meeting of Japanese Circulation Society
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
  • Int'l Joint Research / Invited
• [Presentation] Activation of Mitochondrial ERK1/2 is Involved in an Intracellular Renin-mediated Ischemic Resistance in Diabetic Hearts (2017)
  • Author(s): Satoh T, Saotome M, Ohtani H, Urushida T, Satoh H, Hayashi H.
  • Organizer: The 81th Annual Meeting of Japanese Circulation Society
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
  • Int'l Joint Research
• [Presentation] Alterations in Left Ventricular (LV) Flow Dynamics in Patients with Intra-LV Thrombus: Analysis with 3D-Cine Phase Contrast MRI (4D-Flow) (2017)
  • Author(s): Sakakibara T, Suwa K, Saitoh T, Takehara Y, Kaneko Y, Sakakibara T, Sano M, Saotome M, Urushida T, Katoh H, Satoh H, Sakahara H, Hayashi H.
  • Organizer: The 81th Annual Meeting of Japanese Circulation Society
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
  • Int'l Joint Research
• [Presentation] AMPK-activated Protein Kinase/Dynamin-related Protein-1 Pathway Contributes to Eicosapentaenoic Acid-mediated Cardiac Protection against Lipotoxicity (2017)
  • Author(s): Sakamoto A, Saotome M, Satoh T, Urushida T, Satoh H, Hayashi H.
  • Organizer: The 81th Annual Meeting of Japanese Circulation Society
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
  • Int'l Joint Research
• [Presentation] Measurements of tissue oxygen and hemoglobin on a near infra-red spectroscopy in emergency patients with poor general conditions. (2015)
  • Author(s): Saitoh T, Kanayama N, Niwayama M, Satoh H, Takahashi Y, Hozumi H, Uchida T, Hayashi H, MD, Yoshino A:
  • Organizer: American Heart Association, Scientific Session 2015
  • Place of Presentation: オーランド、米国
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] Alterations in Flow Patterns and Wall Shear Stress in Pulmonary Artery Visualized with Phase-resolved 3D Cine Phase Contrast MRI (4D-Flow) in Patients with Systemic Sclerosis. (2015)
  • Author(s): Sakakibara T, Suwa K, Saitoh T, Takehara Y, Sano M, Saotome M, Urushida T, Katoh H, Satoh H, Alley M, Sakahara H, Hayashi H
  • Organizer: American Heart Association, Scientific Session 2015
  • Place of Presentation: オーランド、米国
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] Acute Hemodynamic Effects of Adaptive-servo Ventilation with Deep Sedation during Pulmonary Vein Isolation (2015)
  • Author(s): Sano M, Satoh H, Suwa K, Saitoh T, Saotome M, Urushida T, Katoh H, Hayashi H.
  • Organizer: 第7９回日本循環器学会総会・学術集会.
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-26
• [Presentation] Subclinical Changes of Flow Dynamics in Pulmonary Artery Visualized with Phase-Resolved 3D Cine Phase Contrast MRI (4D-Flow) in Systemic Scleroderma (2015)
  • Author(s): Ｓｕｗａ Ｋ， Ｓａｎｏ Ｍ， Ｓａｉｔｏｈ Ｔ， Ｓａｏｔｏｍｅ Ｍ， Ｕｒｕｓｈｉｄａ Ｔ， Ｋａｔｏｈ Ｈ， Ｓａｔｏｈ Ｈ， Ｈａｙａｓｈｉ Ｈ
  • Organizer: 第7９回日本循環器学会総会・学術集会.
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-26
• [Presentation] Clinical Features in Sarcoidosis Patients who had Late Gadolinium Enhancement but did not Fulfill the Diagnostic Criteria of Cardiac Involvement (2015)
  • Author(s): Sano M, Satoh H, Suwa K, Saitoh T, Saotome M, Urushida T, Katoh H, Hayashi H.
  • Organizer: 第7９回日本循環器学会総会・学術集会.
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] More effective chest compression and less rescuer fatigue in cardiopulmonary resuscitation by leg-foot chest compression with a footstool (2015)
  • Author(s): Ｓａｉｔｏｈ Ｔ， Sano M, Satoh H, Suwa K, Saitoh T, Saotome M, Urushida T, Katoh H, Hayashi H.
  • Organizer: 第7９回日本循環器学会総会・学術集会.
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Multidisciplinary approach to pregnancy-related acute myocardial infarction (AMI) – Analysis from case reports for 32 years in Japan- (2015)
  • Author(s): Ｓａｔｏｈ Ｈ
  • Organizer: 第7９回日本循環器学会総会・学術集会.
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Eicosapentaenoic acid inhibits palmitate-induced lipotoxicity via a suppression of dynamin-related protein 1 (Drp1) in differentiated H9c2 myocytes (2015)
  • Author(s): Sakamoto A, Saotome M, Satoh T, Nonaka D, Urushida T, Katoh H, Satoh H, Hayashi H
  • Organizer: The 79th meeting of Japanese Circulation Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] Multidisciplinary approach to pregnancy-related acute myocardial infarction (AMI) &#8211; Analysis from case reports for 32 years in Japan- (2015)
  • Author(s): Satoh H, Sano M, Suwa K, Saotome M, Urushida T, Katoh H, Hayashi H
  • Organizer: The 79th meeting of Japanese Circulation Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] Microtubule Disorganization Affects the Mitochondrial Permeability Transition Pore in Cardiac Myocytes (2015)
  • Author(s): Kumazawa A, Katoh H, Nonaka D, Watanabe T, Saotome M, Urushida T, Satoh H, Hayashi H
  • Organizer: The 79th meeting of Japanese Circulation Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Book] 析患者診療に役立つ診断と重症度判定のためのアプローチ (2016)
  • Author(s): 佐藤 洋
  • Total Pages: 321
  • Publisher: 日本メディカルセンター