ATF6 inhibition suppresses the protective effects of pasireotide in human and bovine endothelial cells.

Activating transcription factor 6 (ATF6) is an unfolded protein response sensor with a significant role in endothelial integrity and barrier function. This study investigates the effects of Ceapin-A7, which is an ATF6 inhibitor, in mediating the protective effects of pasireotide (PAS) in the endothelium. Ceapin-A7 suppressed PAS-induced glucose-regulated protein 94 (GRP94) augmentation, cofilin deactivation, and MLC2 dephosphorylation. Furthermore, ATF6 inhibition counteracted the anti-oxidative and anti-inflammatory effects of PAS in human and bovine lung endothelial cells, as evidenced by increased ROS generation and suppression of pSTAT1, pSTAT3, pERK1/2, and pP38. Our study adds information on the protective actions of pasireotide in endothelial cells and supports ongoing efforts to enrich our knowledge of the pathophysiology of sepsis and lung injury.