Inhibition of ox‐LDL‐induced endothelial cell injury by LINC02381 knockdown through the microRNA‐491‐5p/transcription factor 7 axis

Abstract

AbstractAtherosclerosis (AS) is a complex multifactorial and chronic inflammatory vascular disease that contributes to the development of cardiovascular diseases. Abnormal cellular proliferation in human umbilical vein endothelial cells (HUVECs) is a crucial element in AS development. In this study, we investigated the potential role of the long noncoding RNA LINC02381/microRNA (miR)‐491‐5p/transcription factor 7 (TCF7) axis in regulating HUVEC injury in 30 participants suffering from AS and 30 healthy control participants. We established an in vitro model of AS in HUVECs using oxidized low‐density lipoprotein (ox‐LDL), and measured cellular mRNA and protein levels of LINC02381, miR‐491‐5p, and TCF7 in serum samples using reverse transcription‐quantitative polymerase chain reaction and Western blotting assays. We evaluated cell viability, apoptosis, and inflammation using Cell Counting Kit‐8, flow cytometry, and enzyme‐linked immunosorbent assays, respectively. Moreover, we analyzed apoptosis‐related protein expression using western blotting analysis and determined the association between miR‐491‐5p and LINC02381 or TCF7 using dual‐luciferase reporter assay, RNA pull‐down, and rescue experiments. We observed that LINC02381 was elevated, while miR‐491‐5p was downregulated in serum samples from participants with AS and in ox‐LDL‐treated HUVECs. LINC02381 knockdown was protective against HUVEC injury via miR‐491‐5p inhibition, which is its downstream target. Rescue experiments further demonstrated that miR‐491‐5p alleviated HUVEC injury by modulating TCF7. Thus, LINC02381 knockdown ameliorated HUVEC injury by regulating the miR‐491‐5p/TCF7 axis, which provides new insights into AS treatment strategies.