Author + information
- Received January 3, 2020
- Revision received July 27, 2020
- Accepted July 27, 2020
- Published online September 28, 2020.
- Jamie Francisco, MSa,
- Yu Zhang, MSa,
- Jae Im Jeong, BSa,
- Wataru Mizushima, MD, PhDa,
- Shohei Ikeda, MD, PhDa,
- Andreas Ivessa, PhDa,
- Shinichi Oka, PhDa,
- Peiyong Zhai, MD, PhDa,
- Michelle D. Tallquist, PhDb and
- Dominic P. Del Re, PhDa,∗ ()
- aDepartment of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey
- bCenter for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii
- ↵∗Address for correspondence:
Dr. Dominic P. Del Re, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB G-609, Newark, New Jersey 07103.
• YAP is activated by myocardial infarction or neuroendocrine stimulation in cardiac fibroblasts.
• Active YAP promotes TEA domain transcription factor-1–mediated transcription of myocardin-related transcription factor A to facilitate cardiac myofibroblast differentiation and extracellular matrix gene expression.
• Cardiac fibroblast YAP knockout mice have attenuated cardiac fibrosis and dysfunction in response to myocardial infarction.
Fibrotic remodeling of the heart in response to injury contributes to heart failure, yet therapies to treat fibrosis remain elusive. Yes-associated protein (YAP) is activated in cardiac fibroblasts by myocardial infarction, and genetic inhibition of fibroblast YAP attenuates myocardial infarction–induced cardiac dysfunction and fibrosis. YAP promotes myofibroblast differentiation and associated extracellular matrix gene expression through engagement of TEA domain transcription factor 1 and subsequent de novo expression of myocardin-related transcription factor A. Thus, fibroblast YAP is a promising therapeutic target to prevent fibrotic remodeling and heart failure.
This study was supported by National Institutes of Health grants HL127339 and HL135726 (to Dr. Del Re). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The 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 January 3, 2020.
- Revision received July 27, 2020.
- Accepted July 27, 2020.
- 2020 The Authors