ABSTRACT

Objectives: Maturation of dendritic cells (DCs) contributes to atherosclerosis (AS) development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that is involved in tumorigenesis. This study was designed to explore the role of exosomes from oxidized low-density lipoprotein (oxLDL)-treated vascular endothelial cells (VECs) in regulating DCs maturation in AS, and to elucidate whether MALAT1 was involved in this process.

Methods: Human umbilical VECs (HUVECs) were treated with or without ox-LDL, after which exosomes were isolated and then co-cultured with immature DCs (iDCs). The phenotypic profile and cell endocytosis in DCs were examined to assess the degree of maturation of DCs. The interaction between MALAT1 and NRF2 protein in DCs was evaluated using RNA pull-down assay and RNA immunoprecipitation. A mouse model of AS was eatablished by feeding ApoE knockout (ApoE−/-) mice with a high-fat diet for 12 weeks.

Results: The ox-LDL-HUVECs-Exos exhibited lower MALAT1 expression when compared with HUVECs-Exos. Furthermore, exosomes from ox-LDL-treated MALAT1-overexpressing-HUVECs (ox-LDL-HUVECs-ExosLv-MALAT1) released elevated expression of MALAT1 to iDCs, which interacted with NRF2 and activated NRF2 signaling, and thereby inhibited ROS accumulation and DCs maturation. Further in vivo experiments showed that a decrease in MALAT1 content in mouse VECs-Exos might be associated with mouse AS progression.

Conclusion: Loss of exosomal MALAT1 from ox-LDL-treated VECs induces DCs maturation in atherosclerosis development.