Impact of HMGB1 on left ventricular remodeling after myocardial infarction : Novel therapeutic target for neovascularization

• Project/Area Number: 21590923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Yamagata University
• Principal Investigator: KUBOTA Isao 山形大学, 医学部, 教授 (30161673)
• Co-Investigator(Kenkyū-buntansha): WATANABE Tetsu 山形大学, 医学部, 講師 (40359568)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: HMGB-1 / 心筋虚血 / 心肥大 / 心筋梗塞 / HMGB1 / 血管新生

Research Abstract

High Mobility Group Box 1 (HMGB1) is an abundant and ubiquitous nuclear DNA-binding protein that has multiple functions dependent on its cellular location. In the nucleus, HMGB1 binds to DNA, facilitating numerous nuclear functions including maintenance of genome stability, transcription and repair. However, little is known about the effects of nuclear HMGB1 on cardiac hypertrophy and heart failure. The aim of this study was to examine whether nuclear HMGB1 modifies the development of cardiac hypertrophy induced by pressure overload. Thoracic transverse aortic constriction (TAC) was created in transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-TG) and wild type (WT) mice. Cardiac hypertrophy after TAC was attenuated in HMGB1-TG mice and survival rate after TAC was higher in HMGB1-TG mice than in WT mice. Induction of fetal cardiac genes was decreased in HMGB1-TG mice than in WT mice. Nuclear HMGB1 expression was preserved in HMGB1-TG mice compared with WT mice after TAC. Preserved nuclear HMGB1 expression significantly attenuated histone deacetylase (HDAC) activity and DNA damage after TAC. In conclusion, these results suggest that preserved nuclear HMGB1 prevents hypertrophy and heart failure via repressing HDAC activity and DNA damage.

Research Products

• [Journal Article] Prognostic value of low left atrial appendage wall velocity in patients with ischemic stroke and atrial fibrillation (2012)
  • Author(s): Tamura H, Watanabe T, Nishiyama S, Sasaki S, Wanezaki M, Arimoto T, Takahashi H, Shishido T, Miyashita T, Miyamoto T, Kubota I
  • Journal Title: J Am Soc Echocardiogr Volume: 25 Pages: 576-583
  • URL: http://dx.doi.org/10.1016/j.echo.2012.01.012
  • Peer Reviewed
• [Journal Article] Elevated cystatin C levels predict the incidence of vasospastic angina (2011)
  • Author(s): Funayama A, Watanabe T, Tamabuchi T, Otaki Y, Netsu S, Hasegawa H, Honda S, Ishino M, Arimoto T, Takahashi H, Shishido T, Miyamoto T, Nitobe J, Kubota I
  • Journal Title: Circ J Volume: 75 Pages: 2439-2444
  • NAID: 10029459648
  • URL: http://dx.doi.org/10.1253/circj.CJ-11-0008
  • Peer Reviewed
• [Journal Article] Increased left atrial volume index predicts a poor prognosis in patients with heart failure (2011)
  • Author(s): Tamura H, Watanabe T, Nishiyama S, Sasaki S, Arimoto T, Takahashi H, Shishido T, Miyashita T, Miyamoto T, Nitobe J, Hirono O, Kubota I
  • Journal Title: J Card Fail Volume: 17 Pages: 210-216
  • URL: http://dx.doi.org/10.1016/j
  • Peer Reviewed
• [Journal Article] 8-Hydroxy-2'-deoxyguanosine is a prognostic mediator for cardiac event (2011)
  • Author(s): Suzuki S, Shishido T, Ishino M, Katoh S, Sasaki T, Nishiyama S, Miyashita T, Miyamoto T, Nitobe J, Watanabe T, Takeishi Y, Kubota I
  • Journal Title: Eur J Clin Invest Volume: 41 Pages: 759-766
  • URL: http://dx.doi.10.1111/j.1365-2362.2010.02465.x
  • Peer Reviewed
• [Journal Article] Serum pregnancy-associated plasma protein a in patients with heart failure (2011)
  • Author(s): Akira Funayama
  • Journal Title: J Card Fail Volume: 17 Issue: 10 Pages: 819-819
  • DOI: 10.1016/j.cardfail.2011.05.011
  • Peer Reviewed
• [Journal Article] Suppressive effects of valsartan on microalbuminuria and CRP in patients with metabolic syndrome (Val-Mets) (2011)
  • Author(s): Tetsuro Shishido
  • Journal Title: Clin Exp Hypertens. Volume: 33 Issue: 2 Pages: 117-117
  • DOI: 10.3109/10641963.2010.531837
  • Peer Reviewed
• [Journal Article] 8-Hydroxy-2'-deoxyguanosine is a prognostic mediator for cardiac event (2011)
  • Author(s): Satoshi Suzuki
  • Journal Title: Eur J Clin Invest Volume: 41 Pages: 759-759
  • Peer Reviewed
• [Journal Article] 8-Hydroxy 2-deoxyguanosine is a prognostic mediator for cardiac event. (2011)
  • Author(s): Suzuki S
  • Journal Title: Eur J Clin Invest.
  • Peer Reviewed
• [Journal Article] Trends in coronary risk factors among patients with acute myocardial infarction over the last decade : the Yamagata AMI registry (2010)
  • Author(s): Nishiyama S, Watanabe T, Arimoto T, Takahashi H, Shishido T, Miyashita T, Miyamoto T, Nitobe J, Shibata Y, Konta T, Kawata S, Kato T, Fukao A, Kubota I
  • Journal Title: J Atheroscler Thromb Volume: 17 Pages: 989-998
  • NAID: 130004444462
  • URL: http://dx.doi.org/10.5551/jat.4671
  • Peer Reviewed
• [Journal Article] Serum midkine as a predictor of cardiac events in patients with chronic heart failure. (2010)
  • Author(s): Kitahara T
  • Journal Title: J Card Fail. Volume: 16 Pages: 308-308
  • Peer Reviewed
• [Journal Article] High serum level of neopterin is a risk factor of patients with heart failure. (2010)
  • Author(s): Sasaki T
  • Journal Title: Int J Cardiol. Volume: 145 Pages: 318-318
  • Peer Reviewed
• [Journal Article] High serum level of neopterin is a risk factor of patients with heart failure. (2010)
  • Author(s): Sasaki T, et al
  • Journal Title: Int J Cardiol
  • Peer Reviewed
• [Journal Article] High variability of albuminuria in nondiabetic population : the Takahata Study. (2009)
  • Author(s): Suzuki K, et al
  • Journal Title: Clin Exp Nephrol 13 Pages: 452-452
  • Peer Reviewed
• [Journal Article] Combination of conventional biomarkers for risk stratification in chronic heart failure. (2009)
  • Author(s): Niizeki T, et al
  • Journal Title: J Cardiol 53 Pages: 179-179
  • Peer Reviewed
• [Presentation] Pentraxin 3 is essential for neointima formation after vascular injury (2012)
  • Author(s): Ishino M, Shishido T, Suzuki S, Katoh S, Sasaki T, Netsu S, Funayama A, Tamura H, Nishiyama S, Arimoto T, Takahashi H, Miyashita T, Miyamoto T, Watanabe T, Takeishi Y, Kubota I
  • Organizer: The 76th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka, Fukuoka International Congress Center
• [Presentation] Cardiac-specific overexpression of high mobility group box 1 (HMGB1) prevents cardiac dysfunction induced by pressure overload (2012)
  • Author(s): Funayama A, Shishido T, Ishino M, Ohtaki Y, Netsu S, Hasegawa H, Honda S, Kadowaki S, Narumi T, Nishiyama S, Arimoto T, Takiahashi H, Miyashita T, Miyamoto T, Watanabe T, Kubota I
  • Organizer: The 76th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka, Fukuoka International Congress Center
• [Presentation] Overexpression of midkine aggravates cardiac dysfunction and adverse myocardial remodeling induced by pressure overload (2012)
  • Author(s): Netsu S, Shishido T, Ishino M, Funayama A, Kadowaki S, Narumi T, Ohtaki Y, Hasegawa H, Honda S, Tamura H, Nishiyama S, Arimoto T, Takahashi H, Miyashita T, Miyamoto T, Watanabe T, Kubota I
  • Organizer: The 76th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka, Fukuoka International Congress Center
• [Presentation] Cardiac-Specific Overexpression of High Mobility Group Box 1 (HMGB1) Attenuates Cardiac Dysfunction Induced By Pressure Overload (2011)
  • Author(s): Akira Funayama
  • Organizer: AHA scientific meeting
  • Place of Presentation: Orlando (America)
  • Year and Date: 2011-11-13
• [Presentation] Deficiency of the long pentraxin PTX3 deteriorates neointimal hyperplasia after vascular injury (2011)
  • Author(s): Ishino M, Shishido T, Suzuki S, Katoh S, Sasaki T, Netsu S, Funayama A, Arimoto T, Nishiyama S, Takahashi H, Miyashita T, Miyamoto T, Watanabe T, Takeishi Y, Kubota I
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando ,America
• [Presentation] Midkine exacerbates cardiac hypertrophy and remodeling in response to pressure overload (2011)
  • Author(s): Netsu S, Shishido T, Ishino M, Kadowaki S, Narumi T, Otaki Y, Funayama A, Honda S, Hasegawa H, Nishiyama S, Takahashi H, Arimoto T, Miyashita T, Miyamoto T, Watanabe T, Kubota I
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando , America
• [Presentation] Cardiac-specific overexpression of high mobility group box 1 (HMGB1) attenuates cardiac dysfunction induced by pressure overload (2011)
  • Author(s): Funayama A, Shishido T, Netsu S, Ishino M, Otaki Y, Honda S, Hasegawa H, Kadowaki S, Narumi T, Nishiyama S, Takahashi H, Arimoto T, Miyashita T, Miyamoto T, Watanabe T, Woo CH, Kuwahara K, Nakao K, Takeishi Y, Kubota I
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, America
• [Presentation] A comparison of B-type natriuretic peptide and heart-type fatty acid binding protein as predictors of cardiac events in heart failure patients with chronic kidney disease. (2010)
  • Author(s): Ishino M
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-13
• [Presentation] Atrial endothelial impairment through toll-like receptor-4 signaling may cause atrial thrombogenesis (2010)
  • Author(s): Kato S, Watanabe T, Suzuki S, Ishino M, Sasaki T, Shishido T, Sadahiro M, Kubota I
  • Organizer: XXth World Congress of the International Society for Heart Research 2010, Kyoto
  • Place of Presentation: Kyoto International Conference Center
• [Book] Brugada症候群 (2012)
  • Author(s): 渡邉哲, 久保田功
  • Publisher: 循環器疾患最新の治療