LncRNA H19 Promotes Ox-LDL-Induced Dysfunction of Human Aortic Endothelial Cells through the miR-152/VEGFA Axis.

Abstract

Objective lncRNA H19 (H19) elevation is related to the risk of coronary artery disease. DIANA-lncBase database analysis suggested that microRNA-152 (miR-152) and H19 have binding sites. Here, the effect and mechanism of H19 and miR-152 in the oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) were explored. Methods The expression of H19, miR-152, and vascular endothelial growth factor (VEGF)-A in the HAECs treated with 5 μg/mL ox-LDL was detected by qRT-PCR. MTT, wound-healing assay, and tube formation assay were analyzed to evaluate the angiogenic activity of H19 and miR-152 in the HAECs cells knocked down H19. Dual-luciferase assay was performed to verify the targeting relationship of miR-152 to either H19 or VEGFA, respectively. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and vimentin) and VEGFA protein in the cells. Results After ox-LDL treatment, the expression of H19 and VEGFA was significantly increased, miR-152 expression was remarkably decreased. H19 was mainly expressed in the cytoplasm of HAECs. Knocking down H19 or overexpression of miR-152 significantly inhibited the cellular proliferation, migration, tube formation, and EMT trend of the HAECs. On the contrary, miR-152 interference reversed H19 silencing-mediated effects in the ox-LDL-induced HAECs. The dual-luciferase assay showed that miR-152 had a targeting relationship with H19 and VEGFA. MiR-152 was negatively corrected with the VEGFA expression. Conclusion Ox-LDL negatively regulates miR-152 via H19, promotes the expression of VEGFA, and induces the dysfunction of HAECs.