RETRACTED ARTICLE: Loss of exosomal MALAT1 from ox-LDL-treated vascular endothelial cells induces maturation of dendritic cells in atherosclerosis development

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-Exos Lv-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.

Peer Review #1 of "Definition and review on a category of long non-coding RNA: Atherosclerosis-associated circulating lncRNA (ASCLncRNA) (v0.2)"

“…ECs compared with the normal ECs (Li et al 2019). This difference suggests that the role of MALAT1 in AS remains unclear and deserves a multi-center investigation.…”

Definition and review on a category of long non-coding RNA: Atherosclerosis-associated circulating lncRNA (ASCLncRNA)

“…We hypothesize that the high expression of MALAT1 in serum and exosomes originates from the cells surrounding pathological tissues and thus cause a decline in plaques. However, Li and colleagues found lower expression of MALAT1 in exosomes of ox-LDL-treated ECs compared with the normal ECs ( Li et al, 2019 ). This difference suggests that the role of MALAT1 in AS remains unclear and deserves a multi-center investigation.…”

The Role of Exosomal Non-Coding RNAs in Coronary Artery Disease

“…Recent studies have shown that autophagy plays a vital role in the behavior of vascular cells, such as ECs and VSMCs. Li et al found that exosomal miR-221/222 derived from human aortic smooth muscle cells (HAOSMCs) inhibits autophagy in HUVECs by partly regulating the PTEN/Akt signaling pathway when HUVECs and HAOSMCs are co-cultured ( Li et al, 2016 ).…”