Author + information
- Received July 9, 2018
- Revision received October 19, 2018
- Accepted November 19, 2018
- Published online April 29, 2019.
- Tetsuya Takahashi, MDa,
- Tetsuro Shishido, MD, PhDa,∗ (, )
- Daisuke Kinoshita, MD, PhDa,
- Ken Watanabe, MDa,
- Taku Toshima, MDa,
- Takayuki Sugai, MDa,
- Taro Narumi, MD, PhDa,
- Yoichiro Otaki, MD, PhDa,
- Harutoshi Tamura, MD, PhDa,
- Satoshi Nishiyama, MD, PhDa,
- Takanori Arimoto, MD, PhDa,
- Hiroki Takahashi, MD, PhDa,
- Takuya Miyamoto, MD, PhDa,
- Tetsu Watanabe, MD, PhDa,
- Chang-Hoon Woo, DVM, PhDb,
- Jun-ichi Abe, MD, PhDc,
- Yasuchika Takeishi, MD, PhDd,
- Isao Kubota, MD, PhDa and
- Masafumi Watanabe, MD, PhDa
- aDepartment of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan
- bDepartment of Pharmacology, College of Medicine, Yeungnam University, Daegu, Republic of Korea
- cDepartment of Cardiology - Research, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas
- dDepartment of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan
- ↵∗Address for correspondence:
Dr. Tetsuro Shishido, Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
• HMGB1 is a DNA-binding protein associated with nuclear homeostasis and DNA repair.
• Decreased nuclear HMGB1 expression is observed in human failing hearts, which is associated with cardiomyocyte hypertrophy and fibrosis.
• Cardiac nuclear HMGB1 overexpression ameliorates Ang II–induced pathological cardiac remodeling by inhibiting cardiomyocyte DNA damage and following ataxia telangiectasia mutated activation in mice.
• Ataxia telangiectasia mutated inhibitor treatment provided a cardioprotective effect on Ang II–induced cardiac remodeling in mice.
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.
This study was supported in part by a Grant-in-Aid from the 21st Century of Excellence (COE) and Global COE program of the Japan Society for the Promotion of Science (No. F03), and a grant-in-aid for Scientific Research (18K08025, 18K08059, and 16K09490) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received July 9, 2018.
- Revision received October 19, 2018.
- Accepted November 19, 2018.
- 2019 The Authors