Finerenone Attenuates Myocardial Fibrosis and Pyroptosis in Rats with Myocardial Infarction

Area of Science:

• Cardiovascular Research
• Pharmacology
• Molecular Biology

Background:

• Mineralocorticoid receptor (MR) overactivation exacerbates heart failure (HF) progression post-myocardial infarction (MI).
• Nonsteroidal MR antagonists (MRAs) like Finerenone (FIN) show potential for managing post-MI HF.
• Understanding FIN's mechanism in inhibiting myocardial remodeling is crucial.

Purpose of the Study:

• To investigate the antifibrotic and anti-inflammatory mechanisms of FIN in a rat MI model.
• To elucidate FIN's effects on fibrotic pathways (TGF-β signaling, MMP9/TIMP1 balance) and pyroptosis markers.
• To evaluate FIN's impact on ventricular compliance and overall myocardial remodeling.

Main Methods:

• Establishment of a rat MI model via coronary artery ligation.
• Administration of FIN (10 mg/kg/day) for 2 or 4 weeks.
• Histological analyses (H&E, Masson's staining) and molecular analyses (PCR, Western blot, immunohistochemistry).

Main Results:

• FIN treatment significantly attenuated collagen deposition and reduced pyroptosis markers in both infarcted and noninfarcted myocardial regions.
• FIN suppressed TGF-β signaling and normalized the MMP9/TIMP1 balance, indicating antifibrotic effects.
• FIN reduced cardiomyocyte pyroptosis and improved ventricular compliance, demonstrating dual antifibrotic and antipyroptotic actions.

Conclusions:

• Finerenone exhibits dual antifibrotic and antipyroptotic effects in the post-MI heart.
• FIN's mechanism involves suppressing TGF-β signaling, restoring MMP9/TIMP1 balance, and reducing pyroptosis.
• FIN represents a promising therapeutic strategy for mitigating myocardial remodeling and intervening in heart failure.