LncRNA MALAT1 modulates ox-LDL induced EndMT through the Wnt/β-catenin signaling pathway

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.

The role of lncRNA MALAT1 in cardiovascular disease

“…The SNPs in MALAT1 were associated with CVD risk in a Chinese population . MALAT1 was also found up‐regulated in patients with unstable angina and high‐fat food fed ApoE −/− mice, indicating MALAT1 participated in development of atherosclerosis . Knockdown of MALAT1 caused increased plaque size and infiltration of inflammatory CD45 + cells partly via regulation of miR‐503 .…”

“…Knockdown of MALAT1 caused increased plaque size and infiltration of inflammatory CD45 + cells partly via regulation of miR‐503 . Furthermore, MALAT1 were also involved in regulation of endothelial dysfunction, lipid accumulation and chronic inflammation, which contributed to development of atherosclerosis …”

“…Ox‐LDL is considered to be a key factor of initiating and accelerating atherosclerosis and induce the endothelium dysfunction . Ox‐LDL induced MALAT1 and dysfunction of HUVECs by increasing endothelial‐to‐mesenchymal transition (EndMT) via activation of Wnt/β‐catenin signaling, which is common in mouse atherosclerotic lesions and associated with plaque instability in the clinical events . Another study revealed that MALAT1 up‐regulated EndMT expression by sponging miR‐145, which was reported to inhibit SMAD3‐mediated EndMT .…”

“…39 MALAT1 was also found up-regulated in patients with unstable angina and high-fat food fed ApoE −/− mice, indicating MALAT1 participated in development of atherosclerosis. 35,40 Knockdown of MALAT1 caused increased plaque size and infiltration of inflammatory CD45 + cells partly via regulation of miR-503. 41 Furthermore, MALAT1 were also involved in regulation of endothelial dysfunction, lipid accumulation and chronic inflammation, which contributed to development of atherosclerosis.…”

“…41 Furthermore, MALAT1 were also involved in regulation of endothelial dysfunction, lipid accumulation and chronic inflammation, which contributed to development of atherosclerosis. 40,42,43…”