20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells

摘要

Accordingly, we tested the capacity of 20-HETE and a stable analog of this lipid to increase cell survival and decrease apoptosis in BPAECs and ex vivo PAs, and the role of NADPH oxidase-dependent ROS in this protection. In these studies, we show for the first time that 20-HETE enhances survival of PAs and BPAECs through protection from apoptosis. 20-HETE-induced prosurvival effects depend on intact phosphatidylino-sitol 3 (PD)-kinase (PI3K), Akt, and NADPH oxidase pathways. Inhibition of these pathways blocks 20-HETE-induced increases in ROS production, as well as 20-HETE-induced protection from apoptosis. Similarly, inhibition of ROS production blocks 20-HETE-induced protection against apoptosis. These data provide exciting new links between ROS production, NADPH oxidase activity, and activation of PI3K prosurvival pathways. They also raise the possibility that 20-HETE may play an important role in maintaining the integrity of the pulmonary vascular bed through ROS-mediated protection against apoptosis.