Author + information
- Received April 2, 2018
- Revision received November 1, 2018
- Accepted November 2, 2018
- Published online April 29, 2019.
- Chen Gao, PhDa,∗ (, )
- Shuxun Vincent Ren, MD, PhDa,
- Junyi Yu, MDa,b,
- Ulysis Baala,
- Dung Thai, MD, PhDc,d,
- John Lu, MD, PhDc,d,
- Chunyu Zeng, MD, PhDb,
- Hai Yan, PhDc,d and
- Yibin Wang, PhDa,∗ ()
- aDepartment of Anesthesiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
- bDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China
- cREMD Biotherapeutics, Camarillo, California
- dBeijing Cosci-REMD Biotherapeutics, Beijing, China
- ↵∗Address for correspondence:
Dr. Yibin Wang or Dr. Chen Gao, Department of Anesthesiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Drive, Room CHS 37-200J, Los Angeles, California 90095.
• Systemic treatment of an antibody-based glucagon receptor antagonist confers cardioprotection against myocardial infarction and post-myocardial infarction remodeling in mice.
• Systemic treatment of glucagon receptor antagonist prevents pressure overload induced cardiac remodeling and dysfunction in mice.
• Glucagon receptor antagonist treatment attenuates the pathological progression of heart failure induced by pressure overload in mice.
• Long-term suppression of glucagon signaling is potentially an effective therapy for heart failure with different etiologies independent of metabolic disorders.
Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at 4 weeks after myocardial infarction. In addition, REMD2.59 treatment at the onset of pressure overload significantly suppressed cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. Initiation of REMD2.59 treatment 2 weeks after pressure overload significantly blunted the progression of cardiac pathology. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to ameliorate both onset and progression of heart failure.
This work is supported in part by National Institutes of Health grants HL140116 to Dr. Wang. Dr. Gao is a recipient of Postdoctoral Fellowship from American Heart Association (17POST33661136). Drs. Thai, Lu, and Yan are employees of REMD Biotherapeutics. Dr. Wang has served as consultant for REMD Biotherapeutics. All other 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 April 2, 2018.
- Revision received November 1, 2018.
- Accepted November 2, 2018.
- 2019 The Authors