Mineralocorticoid receptor (MR) overactivation promotes cardiac fibrosis. We 
studied the ability of the non-steroidal MR antagonist finerenone to prevent 
fibrotic remodeling. In neonatal rat cardiac fibroblasts, finerenone prevented 
aldosterone-induced nuclear MR translocation. Treatment with finerenone 
decreased the expression of connective tissue growth factor (CTGF) (74 ± 15% of 
control, p = 0.005) and prevented aldosterone-induced upregulation of CTGF and 
lysyl oxidase (LOX) completely. Finerenone attenuated the upregulation of 
transforming growth factor ß (TGF-ß), which was induced by the Rac1 GTPase 
activator l-buthionine sulfoximine. Transgenic mice with cardiac-specific 
overexpression of Rac1 (RacET) showed increased left ventricular (LV) 
end-diastolic (63.7 ± 8.0 vs. 93.8 ± 25.6 µl, p = 0.027) and end-systolic 
(28.0 ± 4.0 vs. 49.5 ± 16.7 µl, p = 0.014) volumes compared to wild-type FVBN 
control mice. Treatment of RacET mice with 100 ppm finerenone over 5 months 
prevented LV dilatation. Systolic and diastolic LV function did not differ 
between the three groups. RacET mice exhibited overactivation of MR and 11ß 
hydroxysteroid dehydrogenase type 2. Both effects were reduced by finerenone 
(reduction about 36%, p = 0.030, and 40%, p = 0.032, respectively). RacET mice 
demonstrated overexpression of TGF-ß, CTGF, LOX, osteopontin as well as collagen 
and myocardial fibrosis in the left ventricle. In contrast, expression of these 
parameters did not differ between finerenone-treated RacET and control mice. 
Finerenone prevented left atrial dilatation (6.4 ± 1.5 vs. 4.7 ± 1.4 mg, 
p = 0.004) and left atrial fibrosis (17.8 ± 3.1 vs. 12.8 ± 3.1%, p = 0.046) 
compared to vehicle-treated RacET mice. In summary, finerenone prevented from 
MR-mediated structural remodeling in cardiac fibroblasts and in RacET mice. 
These data demonstrate anti-fibrotic myocardial effects of finerenone.