Phloretin alleviates palmitic acid-induced oxidative stress in HUVEC cells by suppressing the expression of LncBAG6-AS

Oxidative stress (OS) is an important trigger of vascular endothelial injury (VEI), which then leads to cardiovascular disease (CVDs). Phloretin was previously investigated to alleviate OS in human umbilical vein endothelial cells (HUVECs) by activating the AMPK/Nrf2 pathway; however, whether phloretin exerts cardiovascular health benefits by targeting non-coding RNAs (ncRNAs) remains unclear. Herein, the whole transcriptome sequencing and lncRNA library building were performed on HUVECs, a commonly used cell line for CVDs study, from different groups in control (CK), palmitic acid (PA, 100 mu M), and PA + phloretin (50 mu M, G50). KEGG analysis demonstrated that DE-lncRNAs regulated the pathway related to OS and metabolism in HUVECs. LncBAG6-AS was highly expressed under OS stimulation, which was reversed by phloretin co-treatment. Moreover, the MMP, activities of SOD, GSH-Px, T-AOC and GR were significantly ameliorated after interference of LncBAG6-AS, which were consistent with phloretin recover group. Furthermore, the expression of DE-genes from previously reported mRNA sequencing, including MAPK10, PIK3R1, ATP2B4, AKT2, and ADCY9, were significantly changed with LncBAG6-AS interference, indicating that LncBAG6-AS may participate in the process of OS attenuation by phloretin through regulating gene expression. So, the transcriptome sequencing of HUVECs with LncBAG6-AS knockdown was subsequently performed and DE-genes for "NC vs. si-ASO-LncBAG6-AS" were significantly enriched with GO terms, such as apoptosis, response to OS, ferroptosis, and others, which were similar to those observed from KEGG analysis. Overall, this study provides new insights into the molecular mechanisms by which bioactive substances alleviate OS and potential targets for the early prevention and treatment of VEI. Inhibition of LncBAG6-AS regulated by phloretin alleviates palmitic acid-induced oxidative stress injury in HUVEC cells.