Cellular Mechanisms and Therapeutic Targeting of Long Noncoding <scp>RNAs</scp> in Atherosclerotic Disease

Abstract

To effectively combat atherosclerotic diseases, it is essential to identify novel biomarkers and therapeutic targets that can detect early-stage atherosclerosis before the development of high-risk, unstable plaques. Due to their distinct chemical and biological characteristics, long noncoding RNAs (lncRNAs) have emerged as promising biomarkers for various diseases. This review highlights the potential therapeutic intervention targeting lncRNAs in atherosclerosis. Recent research has pointed out the significant role of lncRNAs in the pathogenesis and progression of atherosclerosis, influencing endothelial dysfunction in both proliferation and migration, lipid metabolism, and plaque stability through diverse molecular mechanisms such as NEAT1, lincRNA-p21, MALAT1, H19, GAS5, MEG3, HOTAIR, and TUG1. This study also emphasizes the role of lncRNAs in the diagnosis and prognosis of atherosclerosis, such as APPAT, MALAT1, MIAT, SOX2-OT, HIF1A-AS1, lncRNA-ATB, PVT1, NORAD, HOTAIR, H19, LIPCAR, and DANCR. The research highlighted the therapeutic intervention targeting various lncRNAs in atherosclerosis via different signaling pathways, such as TNF-α, JAK/STAT, IFN-γ signaling, ROCK1, AP1, and NF-κB signaling, PI3K/AKT/mTOR, which holds a new class of RNA-based therapeutics. The research aims to elucidate the crucial roles of lncRNAs in regulating gene expression and cellular processes involved in atherosclerosis development, which could emerge as potential therapeutic targets for atherosclerosis.