Heart Failure With Reduced Ejection Fraction Is Characterized by Systemic NEP Downregulation

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.