TIGAR control myocardial energy metabolism flexibility and Apoptosis.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790773
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Doshisha University (2013-2014); Kyoto Prefectural University of Medicine (2012)
• Principal Investigator: MITA Yuichiro 同志社大学, 研究開発推進機構, 特別研究員 (70609122)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 心不全 / エネルギー代謝 / TAC / TIGAR

Outline of Final Research Achievements

In spite of the metabolic alterations in heart failure (HF), only recently have the mechanisms underlying these changes been identified. TIGAR reduces glycolysis, but its role on HF is unclear. To investigate the role of TIGAR, we performed TAC-operation. After 4 weeks of TAC, LV function in WT mice was decrease, but not seen in TIGAR KO mice. Next, we used TIGAR conditional KO mouse and a tamoxifen inducible KO mouse. 4 weeks after TAC, LV contraction was preserved in tamoxifen pretreated TIGARflox/flox;MerCreMer with low grade fibrosis. TIGARflox/flox;MerCreMer+ exhibited up-regulation of glucose utilization, high energy phosphate(HEP), and autophagic flux. To evaluate on late phase HF, we treated with tamoxifen 2 weeks after TAC, followed by analysis at 8 weeks. LV dysfunction was also reduced in tamoxifen mid-treated TIGARflox/flox;MerCreMer+. TIGAR attenuates adaptive response in HF. Inhibition of TIGAR improved HEP and protected from HF even after the onset of heart failure.

Free Research Field

代謝