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

Imre J Pavo; Noemi Pavo; Nina Kastner; Denise Traxler; Dominika Lukovic; Katrin Zlabinger; Andreas Spannbauer; Martin Riesenhuber; David Lorant; Philipp E Bartko; Georg Goliasch; Martin Hülsmann; Johannes Winkler; Mariann Gyöngyösi

doi:10.1016/j.jacbts.2020.05.011

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

JACC Basic Transl Sci. 2020 Jul 27;5(7):715-726. doi: 10.1016/j.jacbts.2020.05.011. eCollection 2020 Jul.

Affiliations

¹ Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
² Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
³ Department of Anesthesiology, Medical University of Vienna, Vienna, Austria.

Abstract

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.

Keywords: ANP, atrial natriuretic peptide; ARNI; ARNI, angiotensin-receptor neprilysin-inhibitor; BNP, B-type natriuretic peptide; CMRI+LE, cardiac magnetic resonance and late enhancement; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; NEP, neprilysin; NT-proBNP, N-terminal pro-B-type natriuretic peptide; Q1 to Q3, 25th to 75th percentile; RA, right atrial; RV, right ventricular; biomarker; gene expression; left atrial, left atrial; mRNA, messenger RNA; metalloproteinase; neprilysin; qPCR, real-time polymerase chain reaction; translational model of heart failure.