Finerenone ameliorated ventricular remodeling post myocardial infarction in rats by reducing NF-KB pathway-mediated pyroptosis.

Myocardial infarction (MI) remains a leading cardiovascular cause of mortality in patients, primarily driven by adverse post-MI ventricular remodeling tightly linked to inflammation. Finerenone, the first non-steroidal mineralocorticoid receptor (MR) antagonist, is clinically indicated to improve cardiovascular and renal outcomes in patients with chronic kidney disease (CKD) associated with type 2 Diabetes Mellitus (T2DM). Multiple previous studies have validated the robust cardioprotective effects of finerenone post MI. Nevertheless, whether finerenone ameliorates post-MI ventricular remodeling by regulating pyroptosis, an inflammation-associated programmed cell death, and its specific underlying molecular mechanisms remain largely uncharacterized. Male Sprague-Dawley (SD) rats were randomly divided into Sham group, MI group, MI + Spironolactone group and MI + Finerenone group. Compared with MI group, finerenone ameliorated ventricular remodeling and inhibited inflammatory cell infiltration post MI in rats. Meanwhile, finerenone reduced myocardial MR expression, pyroptosis and activation of NF-κB signaling pathway post MI in rats. The in vitro experimental results further showed finerenone could inhibit pyroptosis through MR-activated NF-κB pathway. Finerenone could reduce cardiac inflammation and improve ventricular remodeling post MI probably by decreasing NF-κB signaling pathway mediated pyroptosis via MR, which offer promising a novel therapeutic target for clinical intervention in patients with MI.