Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 4, Issue 2, Pages 234-247Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2018.11.011
Keywords
DNA damage response; HMGB1; pathological cardiac hypertrophy
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Funding
- Japan Society for the Promotion of Science [F03]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [18K08025, 18K08059, 16K09490]
- Grants-in-Aid for Scientific Research [18K08059, 16K09490, 18K08025] Funding Source: KAKEN
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High-mobility group box 1 (HMGB1) is a deoxyribonucleic acid (DNA)-binding protein associated with DNA repair. Decreased nuclear HMGB1 expression and increased DNA damage response (DDR) were observed in human failing hearts. DNA damage and DDR as well as cardiac remodeling were suppressed in cardiac-specific HMGB1 overexpression transgenic mice after angiotensin II stimulation as compared with wild-type mice. In vitro, inhibition of HMGB1 increased phosphorylation of extracellular signal-related kinase 1/2 and nuclear factor kappa B, which was rescued by DDR inhibitor treatment. DDR inhibitor treatment provided a cardioprotective effect on angiotensin II-induced cardiac remodeling in mice. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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