Author + information
- Imre J. Pavo, MDa,
- Noemi Pavo, MD, PhDb,∗ (, )
- Nina Kastner, MDb,
- Denise Traxler, MDb,
- Dominika Lukovic, MSc, PhDb,
- Katrin Zlabinger, MScb,
- Andreas Spannbauer, MDb,
- Martin Riesenhuber, MDb,
- David Lorant, MDc,
- Philipp E. Bartko, MD, PhDb,
- Georg Goliasch, MD, PhDb,
- Martin Hülsmann, MDb,
- Johannes Winkler, MPharm, PhDb,∗ and
- Mariann Gyöngyösi, MD, PhDb,∗
- aDepartment of Pediatrics, Medical University of Vienna, Vienna, Austria
- bDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
- cDepartment of Anesthesiology, Medical University of Vienna, Vienna, Austria
- ↵∗Address for correspondence:
Dr. Noemi Pavo, Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
• The kidneys might play a crucial role in regulating systemic NEP actions based on 20 to 100 higher NEP content and activity of the kidneys compared with any other organ.
• Tissue NEP expression seems to be downregulated and translates into reduced tissue protein concentrations and activity in HF.
• Neither plasma or liquor NEP concentrations and activities reflect tissue NEP regulation; therefore, using NEP as a circulating biomarker seems to be questionable.
Based on the investigation of neprilysin (NEP) regulation in a translational porcine model of chronic heart failure (HF), this study concluded: 1) that kidneys might play a crucial part in systemic NEP regulation based on 20 to 100 higher NEP content and/or activity compared with any other organ; 2) NEP seems to be downregulated under HF conditions; and 3) that the value of plasma NEP concentrations and activity as biomarkers is questionable. For the first time, these data provide basic knowledge on HF-related pathophysiological alterations of the NEP system and contribute to understanding the mechanism of action of angiotensin-receptor neprilysin-inhibitors, which remains elusive despite broad clinical applications.
↵∗ Drs. Winkler and Gyöngyösi contributed equally to this work and are joint senior authors.
The 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 September 30, 2019.
- Revision received May 8, 2020.
- Accepted May 8, 2020.
- 2020 The Authors