oxPAPC-Mediated lncRNA CYP1B1-AS1 From Dendritic Cells Accelerates Atherosclerosis.

Oxidised 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC), dendritic cells (DCs), and long non-coding RNAs (lncRNAs) play crucial roles in atherosclerosis (AS). This study aimed to determine whether oxPAPC-induced DC-derived lncRNAs contribute to AS and to elucidate the underlying regulatory mechanisms. DCs were treated with increasing oxPAPC concentrations to assess transcriptomic changes. RNA sequencing was used to identify differential expression of lncRNAs. ChIP-Seq and RNA pull-down assays were used to assess direct binding between lncRNA CYP1B1-AS1 and NFATC2. The association between CYP1B1-AS1 and CYP1B1 was assessed using Pearson's correlation analysis. Elevated serum oxPAPC levels were confirmed in patients with coronary heart disease. In vitro, sustained oxPAPC stimulation activated the TLR4-MD2 pathway in DCs. CYP1B1-AS1 was identified as the key oxPAPC-induced DC-derived lncRNA, with Gm33055 as its murine homologue. RNA sequencing revealed oxPAPC-driven alterations in DC chemotaxis, differentiation, and lymphocyte activation. Analysis of human atherosclerotic plaque-derived DCs showed significant CYP1B1-AS1 upregulation. Gm33055 enhanced Cyp1b1 expression in murine DCs. Mechanistically, oxPAPC promoted NFATC2 nuclear translocation. NFATC2 binds to the CYP1B1-AS1 promoter, whereas CYP1B1-AS1 directly interacts with NFATC2, forming a positive regulatory loop. Adoptive transfer of m-CYP1B1-AS1-expressing DCs into Apoe(-/-) mice accelerated AS progression. These findings identify a DC-derived lncRNA-mediated regulatory axis that promotes AS and suggest potential therapeutic targets.