High expression of active ATF6 aggravates endoplasmic reticulum stress‑induced vascular endothelial cell apoptosis through the mitochondrial apoptotic pathway.

Activating transcription factor 6 (ATF6), one of three sensor proteins in the endoplasmic reticulum (ER), is an important regulatory factor in the ER stress‑induced apoptosis pathway. Although recent studies have made some progress in elucidating the regulation mechanism of ATF6, the specific regulatory mechanism of ER stress‑induced vascular endothelial cell (VEC) apoptosis is still unclear. The present study was designed to investigate the role of ATF6 in VECs under thapsigargin (TG)‑induced ER stress. ATF6 (1‑366aa; ATF6 high‑expressed plasmid) and ATF6 (151‑366aa; plasmid without transcriptional activity) were transfected into VECs to yield an ATF6 high‑expression model and a positive control model, respectively. High expression of ATF6 decreased viability and aggravated ER stress‑induced apoptosis in VECs. Increased expression of apoptosis‑related genes, including those encoding caspase‑3, caspase‑9, C/EBP homologous protein (CHOP), cytochrome c and B‑cell lymphoma‑associated protein X (Bax)/B‑cell lymphoma (Bcl‑)2, was detected by polymerase chain reaction and western blotting in the ATF6 (1‑366aa) + TG group. No significant effect of TG treatment and high ATF6 expression was indicated on the expression of death receptor‑related genes, including those encoding caspase‑8 and Fas. The results demonstrated that high expression of activated ATF6 aggravates ER stress‑induced VEC apoptosis through the mitochondrial apoptotic pathway. Furthermore, in response to ER stress, ATF6 upregulates the expression of caspase‑3, caspase‑9, CHOP, cytochrome c and Bax/Bcl‑2.