Abstract
BackgroundEndothelial-to-mesenchymal transition (EndMT) plays significant roles in atherosclerosis, but the regulatory mechanisms involving lncRNAs remain to be elucidated. Here we sort to identify the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in ox-LDL-induced EndMT.MethodsThe atherosclerosis model was established by feeding ApoE−/− mice with high-fat diet, and the levels of lncRNA MALAT1 in mouse arterial tissue were detected by RT-qPCR. Cell model was established by treating human umbilical vein endothelial cells (HUVECs) with ox-LDL, and the levels of EndMT markers, such as CD31, vWF, α-SMA and Vimentin and lncRNA MALAT1 levels were detected and their correlations were analyzed. The role of MALAT1 in EndMT and its dependence on Wnt/β-catenin signaling pathway was further detected by knocking down or overexpressing MALAT1.ResultsMALAT1 was upregulated in high-fat food fed ApoE−/− mice. HUVECs treated with ox-LDL showed a significant decrease in expression of CD31 and vWF, a significant increase in expression of α-SMA and vimentin, and upregulated MALAT1. An increased MALAT1 level facilitated the nuclear translocation of β-catenin induced by ox-LDL. Inhibition of MALAT1 expression reversed nuclear translocation of β-catenin and EndMT. Moreover, overexpression of MALAT1 enhanced the effects of ox-LDL on HUVEC EndMT and Wnt/β-catenin signaling activation.ConclusionsOur study revealed that the pathological EndMT required the activation of the MALAT1-dependent Wnt/β-catenin signaling pathway, which may be important for the onset of atherosclerosis.Trial registrationNot applicable.
Highlights
Endothelial-to-mesenchymal transition (EndMT) plays significant roles in atherosclerosis, but the regulatory mechanisms involving lncRNAs remain to be elucidated
We found that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) level was remarkably up-regulated in aortas of model group compared with that of control group (Fig. 1c)
These results indicate that with the dyslipidemia, the level of lncRNA MALAT1 is elevated in the arterial tissue of atherosclerotic mice
Summary
Endothelial-to-mesenchymal transition (EndMT) plays significant roles in atherosclerosis, but the regulatory mechanisms involving lncRNAs remain to be elucidated. Methods: The atherosclerosis model was established by feeding ApoE−/− mice with high-fat diet, and the levels of lncRNA MALAT1 in mouse arterial tissue were detected by RT-qPCR. Cell model was established by treating human umbilical vein endothelial cells (HUVECs) with ox-LDL, and the levels of EndMT markers, such as CD31, vWF, α-SMA and Vimentin and lncRNA MALAT1 levels were detected and their correlations were analyzed. An increased MALAT1 level facilitated the nuclear translocation of β-catenin induced by ox-LDL. As one of the causal risk factors for atherosclerosis, oxidized low-density lipoprotein (ox-LDL) activates the receptor of ox-LDL in endothelial cells [10] to up-regulate stimulators such as inflammatory cytokines [11], ROS [12] and TGF-β [13], which can further induce EndMT. It is reported that ox-LDL could induce MALAT1 transcription through NF-κB pathway in THP-1-derived macrophages [24], and MALAT1 can modulate TGF-β1-induced EndMT in endothelial progenitor cells [25]
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