PCSK9 inhibitor attenuates cardiac fibrosis in reperfusion injury rat by suppressing inflammatory response and TGF-β1/Smad3 pathway.

Progressive cardiac fibrosis, a hallmark of heart failure, remains poorly understood regarding Proprotein convertase subtilisin/kexin type 9 (PCSK9) 's role. This study aims to elucidate PCSK9's involvement in cardiac fibrosis. After ischemia/reperfusion (I/R) injury surgery in rats, PCSK9 inhibitors were used to examine their effects on the transforming growth factor-β1 (TGF-β1)/small mother against decapentaplegic 3 (Smad3) pathway and inflammation. Elevated PCSK9, TGF-β1, and Smad3 levels were observed in cardiac tissues post-I/R injury, indicating fibrosis. PCSK9 inhibition reduced pro-fibrotic protein expression, protecting the heart and mitigating I/R-induced damage and fibrosis. Additionally, it ameliorated cardiac inflammation and reduced post-myocardial infarction (MI) size, improving cardiac function and slowing heart failure progression. PCSK9 inhibitors significantly attenuate myocardial fibrosis induced by I/R via the TGF-β1/Smad3 pathway.