RT info:eu-repo/semantics/article
T1 Benefits of the Non-Steroidal Mineralocorticoid Receptor Antagonist Finerenone in Metabolic Syndrome-Related Heart Failure with Preserved Ejection Fraction
A1 Lima-Posada, Ixchel
A1 Stephan, Yohan
A1 Soulié, Matthieu
A1 Bonnard, Benjamin
A1 Nicol, Lionel
A1 Kolkhof, Peter
A1 Jaisser, Frederic
A1 Mulder, Paul
A1 Palacios-Ramirez, Roberto
K1 diabetes; heart failure; mineralocorticoid receptor antagonist; diastolic dysfunction; finerenone
AB The mineralocorticoid receptor (MR) plays an important role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option, but their use in patients with CKD is limited due to the associated risk of hyperkalemia. Finerenone is a non-steroidal MRA associated with an improved benefit-risk profile in comparison to steroidal MRAs. In this study, we decided to test whether finerenone improves renal and cardiac function in male hypertensive and diabetic ZSF1 rats as an established preclinical HFpEF model. Finerenone was administered at 10 mg/kg/day for 12 weeks. Cardiac function/hemodynamics were assessed in vivo. ZSF1 rats showed classical signs of CKD with increased BUN, UACR, hypertrophy, and fibrosis of the kidney together with characteristic signs of HFpEF including cardiac fibrosis, diastolic dysfunction, and decreased cardiac perfusion. Finerenone treatment did not impact kidney function but reduced renal hypertrophy and cardiac fibrosis. Interestingly, finerenone ameliorated diastolic dysfunction and cardiac perfusion in ZSF1 rats. In summary, we show for the first time that non-steroidal MR antagonism by finerenone attenuates cardiac diastolic dysfunction and improves cardiac perfusion in a preclinical HFpEF model. These cardiac benefits were found to be largely independent of renal benefits.
YR 2023
FD 2023-01-28
LK https://uvadoc.uva.es/handle/10324/65924
UL https://uvadoc.uva.es/handle/10324/65924
LA eng
NO Int J Mol Sci. 2023 Jan 28;24(3).
NO Producción Científica
DS UVaDOC
RD 28-nov-2024