Investigating the Impact of LncRNAs PUNISHER and GAS5 on the Pathogenesis of Calcific Aortic Valve Disease

Abstract

Calcific aortic valve disease (CAVD) is a progressive disorder marked by fibrosis and calcification of the aortic valve, lacking effective pharmacological treatment. This study investigates the roles of two long non-coding RNAs (lncRNAs), PUNISHER and GAS5, in the pathogenesis of CAVD. Through in vitro experiments using human coronary artery endothelial cells (HCAECs), smooth muscle cells (HCASMCs), and valvular interstitial cells (VICs), we explored how these lncRNAs influence endothelial-to-mesenchymal transition (EndMT), osteogenic differentiation, cell proliferation, and apoptosis. Both PUNISHER and GAS5 were found to be upregulated under pro-calcific conditions, while their knockdown significantly reduced EndMT markers and calcification-related genes such as RUNX2, BMP2, and ALPL. Furthermore, proteomic and gene array analyses revealed their regulatory impact on apoptotic and osteogenic signaling pathways. These findings suggest that PUNISHER and GAS5 contribute to CAVD progression and may serve as promising targets for therapeutic intervention.