Abstract 18041: The Novel Mineralocorticoid Receptor Antagonist Finerenone Attenuates Neointima Formation After Vascular Injury
Introduction: Ischemic cardiomyopathy as a result of coronary artery disease is the leading cause for heart failure. Finerenone, a novel nonsteroidal mineralocorticoid receptor (MR) antagonist, holds the promise to be safe and efficient in the treatment of patients with heart failure and/or chronic kidney disease. However, the effects on vascular function remain elusive.
Hypothesis: The aim of this study was to determine the functional effect of selective MR antagonism by Finerenone in vascular cells in vitro and the effect on vascular remodeling following acute vascular injury in vivo.
Methods and Results: Finerenone dose-dependently and significantly reduced aldosterone-induced human coronary artery smooth muscle cell (SMC) proliferation (BrdU incorporation). Furthermore, Finerenone dose-dependently and significantly prevented aldosterone-induced apoptosis in human umbilical vein endothelial cells (EC; FLICA assay).
In vivo, oral application of Finerenone dose-dependently and significantly inhibited intimal and medial cell proliferation following femoral artery wire-induced injury in C57BL/6J mice as quantified by staining for Ki-67 10 days following injury (vehicle vs. 1 mg/kg/d vs. 10mg/kg/d; each p<0.01). Concomitantly, Finerenone attenuated neointimal lesion formation following femoral artery wire-induced injury 21 days following injury (luminal stenosis, vehicle vs. Finerenone 1 mg/kg/d vs. Finerenone 10mg/kg/d: 90.2% ± 1.1% vs. 60.1% ± 17.3%; p=0.1063 to vehicle, vs. 35.3% ± 10.0%; p=0.0061 to vehicle; n=8). Furthermore, Finerenone treatment significantly accelerated the re-endothelialization of injured vessel segments three days following electric injury of the murine carotid artery.
Conclusions: Finerenone treatment significantly attenuates SMC proliferation while simultaneously preventing apoptosis of EC in vitro. This is reflected by a significantly reduced neointima formation and reduction of luminal stenosis as well as a an accelerated endothelial healing of the injured vessels. Thus, apart from its beneficial effects in heart failure therapy, Finerenone might provide favorable vascular effects through restoring vascular integrity and preventing adverse vascular remodeling.
Author Disclosures: D. Sedding: None. R. Musmann: None. J. Dutzmann: None. P. Kolkhof: Employment; Modest; Employee of Bayer Health Care. J. Bauersachs: None.
- © 2016 by American Heart Association, Inc.