Department of Cardiovascular Medicine, Anshun City People's Hospital, Anshun 561000, Guizhou, China.
Department of Hematology, Anshun City People's Hospital, Anshun 561000, Guizhou, China.
Biochem Pharmacol. 2024 Dec;230(Pt 1):116563. doi: 10.1016/j.bcp.2024.116563. Epub 2024 Oct 1.
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.
进行性心肌纤维化是心力衰竭的一个标志，但关于前蛋白转化酶枯草溶菌素/糜蛋白酶 9（PCSK9）在其中的作用仍知之甚少。本研究旨在阐明 PCSK9 在心纤维化中的作用。在大鼠缺血/再灌注（I/R）损伤手术后，使用 PCSK9 抑制剂来研究它们对转化生长因子-β1（TGF-β1）/小母 against decapentaplegic 3（Smad3）通路和炎症的影响。I/R 损伤后心脏组织中 PCSK9、TGF-β1 和 Smad3 水平升高，表明存在纤维化。PCSK9 抑制可降低致纤维化蛋白的表达，保护心脏并减轻 I/R 诱导的损伤和纤维化。此外，它还可改善心脏炎症，减少心肌梗死后（MI）的面积，从而改善心脏功能并减缓心力衰竭的进展。PCSK9 抑制剂通过 TGF-β1/Smad3 通路显著减轻 I/R 引起的心肌纤维化。
