What does this research mean for the field?

oxPAPC-induced lncRNA CYP1B1-AS1 from dendritic cells accelerates atherosclerosis progression. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

The research examines how oxPAPC-induced lncRNAs from dendritic cells impact atherosclerosis and the regulatory mechanisms involved.

March 2, 20260 citations

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

CYCheng YanDonghua University LNLang NiZunyi Medical University CKChanghao KeArmy Medical University

Key Points

The research examines how oxPAPC-induced lncRNAs from dendritic cells impact atherosclerosis and the regulatory mechanisms involved.
Dendritic cells were treated with varying concentrations of oxPAPC to observe transcriptomic changes.
RNA sequencing was conducted to identify differentially expressed lncRNAs.
ChIP-Seq and RNA pull-down assays assessed binding between lncRNA CYP1B1-AS1 and NFATC2.
Pearson's correlation analysis was used to explore the relationship between CYP1B1-AS1 and CYP1B1.
In vitro studies measured the activation of the TLR4-MD2 pathway in dendritic cells.
CYP1B1-AS1 was prioritized as the key lncRNA induced by oxPAPC in dendritic cells.
Increased expression of CYP1B1-AS1 was found in atherosclerotic plaque-derived dendritic cells.
OxPAPC stimulation led to NFATC2 nuclear translocation and binding to the CYP1B1-AS1 promoter.
Adoptive transfer of m-CYP1B1-AS1-expressing dendritic cells into Apoe-/- mice accelerated atherosclerosis progression.

Abstract

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.

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Cite This Study

Yan et al. (Sun,) studied this question.

synapsesocial.com/papers/69a52e26f1e85e5c73bf1851 https://doi.org/https://doi.org/10.1111/jcmm.71066

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