Analysis of metabolic remodeling and mitochondrial function in heart failure

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790790
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: The Tazuke Kofukai
• Principal Investigator: KATO Takao 公益財団法人田附興風会, 医学研究所 第2研究部, 研究員 (30583877)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ミトコンドリア / ミトコンドリア機能 / 悪液質 / 非侵襲的評価 / 心不全

Research Abstract

Although mitochondria play pivotal roles in heart failure, there are few feasible methods for cardiac assessing mitochondrial function in vivo. We validated that the retention of technetium-99m sestamibi (99mTc-MIBI) is useful for assessing cardiac mitochondrial function in vivo and that increased washout (or decreased retention) of 99mTc-MIBI occurs in an animal model of HF and patients with HF, associated with the severity of the disease.
Next, we examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function. The uptake of analogs of glucose or fatty acids and the phosphocreatine/ATP ratio at rest were normal. The levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered, and the capacity of mitochondrial function was decreased.

Research Products

• [Journal Article] Persistent overexpression of phosphoglycerate mutase, a glycolytic enzyme, modifies energy metabolism and reduces stress resistance of heart in mice (2013)
  • Author(s): Okuda J, Niizuma S, Shioi T, Kato T, Inuzuka Y, Kawashima T, Tamaki Y, Kawamoto A, Tanada Y, Iwanaga Y, Narazaki M, Matsuda T, Adachi S, Soga T, Takemura G, Kondoh H, Kita T, Kimura T
  • Journal Title: PLoS One Volume: 8(8) Pages: e72173
  • DOI: 10.1371/journal.pone.0072173
  • Peer Reviewed
• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
  • Peer Reviewed
• [Journal Article] Abnormal liver metabolism and pro-inflammatory responses are modulators of cardiac cachexia in a rat model of heart failure (2013)
  • Author(s): Kato T, Shioi T
  • Journal Title: J Cachexia Sarcopenia Muscle Volume: 4 Pages: 307-308
  • Peer Reviewed
• [Journal Article] Analysis of liver metabolism in a rat model of heart failure (2012)
  • Author(s): Kato T, Niizuma S, Inuzuka Y, Kawashima T, Okuda J, Tamaki Y, Iwanaga Y, Narazaki M, Matsuda T, Soga T, Kita T, Kimura T, Shioi T
  • Journal Title: Int J Cardiol Volume: 161(3) Pages: 130-6
  • Peer Reviewed
• [Journal Article] Tc-99m Sestamibi washout is a useful method to assess cardiac mitochondrial function and the increased risk of a failing heart : A translational approach to understand the metabolic state of the heart (2012)
  • Author(s): Kato T, Shioi T, Kawamoto A, Kimura T, Nagakura D, Nakane E, Miyamoto S, Izumi T, Haruna T, Inoko M, Nohara R
  • Journal Title: Circulation Volume: 126 Pages: A10905
  • URL: http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A10905
  • Peer Reviewed
• [Presentation] A potential linkage between mitochondrial function of the heart and leg muscle in heart failure patients (2014)
  • Author(s): Kato T, Inoko M.
  • Organizer: World Congress of Cardiology Scientific Sessions 2014
  • Place of Presentation: Melboume, Austraria
  • Year and Date: 20140504-07
• [Presentation] Mitochondrial Structural Abnormalities are Common Features in the Myocardium of Patients with Various Types of Cardiomyopathy (2014)
  • Author(s): Kato T, Fukui S, Kimura M, Okano M, Suu K, Morita Y, Minamino E, Nakane E, Miyamoto S, Izumi T, Haruna T, Inoko M
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] Cardiac Cachexia Accompanied with Abnormal Liver Metabolism and Pro-Inflammatory Responses in a Rat Model of Heart Failure (2014)
  • Author(s): Kato T, Niizuma S, Inoko M, Shioi T, Kimura T
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] Abnormal liver metabolism and pro-inflammatory responses are modulators of cardiac cachexia in a rat model of heart failure (2013)
  • Author(s): Kato T, Shioi T
  • Organizer: 7th Cachexia Conference
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20131209-11
• [Presentation] Tc-99m Sestamibi washout is a useful method to assess cardiac mitochondrial function and the increased risk of a failing heart : A translational approach to understand the metabolic state of the heart (2012)
  • Author(s): Kato T, Shioi T, Kawamoto A, Kimura T, Nagakura D, Nakane E, Miyamoto S, Izumi T, Haruna T, Inoko M, Nohara R
  • Organizer: AHA Scientific session
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 20121103-06
• [Presentation] Mitochondrial function as a potential mediator of metabolic remodeling in the heart (2012)
  • Author(s): Kato T, Shioi T, Kawashima T, Kawamoto A, Kimura T.
  • Organizer: ESC Congress 2012
  • Place of Presentation: Munich, Germany
  • Year and Date: 20120825-29