Roles of osteoprotegerin in the development of heart failure/aortic aneurysm

• Project/Area Number: 26461076
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: University of Miyazaki
• Principal Investigator: Tsuruda Toshihiro 宮崎大学, 医学部, 講師 (10389570)
• Co-Investigator(Kenkyū-buntansha): 北村 和雄 宮崎大学, 医学部, 教授 (50204912) ; 畠山 金太 奈良県立医科大学, 医学部, 准教授 (60325735)
• Co-Investigator(Renkei-kenkyūsha): UDAGAWA Nobuyuki 松本歯科大学, 歯学部, 教授 (70245801) ; SEKIMOTO Tomohisa 宮崎大学, 医学部, 助教 (60305000)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心不全 / 骨粗鬆症 / 加齢 / 線維化 / アポトーシス / 高血圧 / アンジオテンシン / 骨粗鬆

Outline of Final Research Achievements

Main purpose of this study was to elucidate the possible roles for osteoprotegerin (OPG) in the development of heart failure. In 52-week-old OPG-/- mice, we found that the OPG-/- mice displayed higher blood pressure than wild-types. In addition, OPG-/- mice revealed left ventricular dilation concomitant with reduction in left ventricular contractility. In histological analysis, OPG-/- mice showed infrequent fibrosis for its heart size. Furthermore, we administered angiotensin II to 8-week-old OPG-/- mice and wild-type mice, and we found the exaggerated left ventricular hypertrophy with the impaired left ventricular contractility. Recombinant OPG to these mice partially improved the phenomena. Taken together, our results suggest that OPG may have additive effects on cardiac structure and function associated with aging and hypertension.

Research Products

• [Journal Article] Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene (2016)
  • Author(s): Hao Y, Tsuruda T, Sekita-Hatakeyama Y, Kurogi S, Kubo K, Sakamoto S, Nakamura M, Udagawa N, Sekimoto T, Hatakeyama K, Chosa E, Asada Y, Kitamura K
  • Journal Title: Cardiovasc Res Volume: 110 Issue: 1 Pages: 62-72
  • DOI: 10.1093/cvr/cvw025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Angiotensin II stimulation of cardiac hypertrophy and functional decompensation in osteoprotegerin-deficient mice. (2016)
  • Author(s): Tsuruda T, Sekita-Hatakeyama Y, Hao Y, Sakamoto S, Kurogi S, Nakamura M, Udagawa N, Funamoto T, Sekimoto T, Hatakeyama K, Chosa E, Kato J, Asada Y, Kitamura K.
  • Journal Title: Hypertension Volume: 67 Issue: 5 Pages: 848-856
  • DOI: 10.1161/hypertensionaha.115.06689
  • Peer Reviewed / Open Access
• [Journal Article] Osteoprotegerin is secreted into the coronary circulation: a possible association with the renin-angiotensin system and cardiac hypertrophy (2014)
  • Author(s): Koyama S, Tsuruda T, Ideguchi T, Kawagoe J, Onitsuka H, Ishikawa T. Date H, Hatakeyama K, Asada Y, Kato J, Kitamura K
  • Journal Title: Horm Metab Res Volume: 46 Issue: 08 Pages: 581-586
  • DOI: 10.1055/s-0034-1375611
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impact of age-dependent adventitia inflammation on structural alteration of abdominal aorta in hyperlipidemic mice (2014)
  • Author(s): Sakamoto S, Tsuruda T, Hatakeyama K, Imamura T, Asada Y, Kitamura K
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Osteoprotegerin, but not Receptor Activator of Nuclear Factor kappaB Ligand, is Associated with the Development of Systolic Heart Failure (2017)
  • Author(s): Tsuruda T, Kitamura K
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] 骨粗鬆症と心不全の接点－オステオプロテゲリンの関与 (2016)
  • Author(s): 鶴田敏博、北村和雄
  • Organizer: 第20回日本心血管代謝内分泌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
• [Presentation] アンジオテンシンIIはオステオプロテゲリン遺伝子欠損マウスの遠心性肥大を促進させる (2016)
  • Author(s): 鶴田敏博、北村和雄
  • Organizer: 第39回日本高血圧学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-30
• [Presentation] Angiotensin II stimulation enhances cardiac hypertrophy and functional decompensation in osteoprotegerin-knockout mice (2016)
  • Author(s): Tsuruda T, Sekita-Hatakeyama Y, Kurogi S, Hao Y, Sakamoto S, Nakamura M, Udagawa N, Sekimoto T, Hatakeyama K, Chosa E, Asada Y, Kitamura K
  • Organizer: European Society of Cardiology Congress 2016
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene (2016)
  • Author(s): Tsuruda T, Hao Y, Kurogi S, Nakamura M, Udagawa N, Chosa E, Asada Y, Kitamura K
  • Organizer: American College of Cardiology. 65th Annual Scientific Session
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene (2016)
  • Author(s): Tsuruda T, Sakamoto S, Hatakeyama K, Asada Y, Kitamura K
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
• [Presentation] Deletion of osteoprotegerin gene exacerbates cardiac hypertrophy and systolic dysfunction in aged-mice (2015)
  • Author(s): Tsuruda T, Hao I, Sakamoto S, Kurogi S, Udagawa N, Nakamura M, Hatakeyama K, Chosa E, Asada Y, Kitamura K
  • Organizer: European Society of Cardiology Congress 2015
  • Place of Presentation: London, UK
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] 高齢者における身体活動度は心筋ストレスや骨代謝マーカーではなく、血清アルブミン濃度によって規定される (2014)
  • Author(s): 鶴田敏博
  • Organizer: 第５６回日本老年医学会学術集会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-06-12 – 2014-06-14