Hypoxia and the integrated stress response promote pulmonary hypertension and preeclampsia: Implications in drug development

Chronic hypoxia is a common cause of pulmonary hypertension, preeclampsia, and intrauterine growth restriction (IUGR). The molec-ular mechanisms underlying these diseases are not completely understood. Chronic hypoxia may induce the generation of reactive oxygen species (ROS) in mitochondria, promote endoplasmic reticu-lum (ER) stress, and result in the integrated stress response (ISR) in the pulmonary artery and uteroplacental tissues. Numerous studies have implicated hypoxia-inducible factors (HIFs), oxidative stress, and ER stress/unfolded protein response (UPR) in the development of pul-monary hypertension, preeclampsia and IUGR. This review high-lights the roles of HIFs, mitochondria-derived ROS and UPR, as well as their interplay, in the pathogenesis of pulmonary hypertension and preeclampsia, and their implications in drug development.

Automated summary

Chronic hypoxia can lead to the generation of reactive oxygen species, endoplasmic reticulum stress, and integrated stress response, playing important roles in the development of pulmonary hypertension, preeclampsia, and intrauterine growth restriction. Hypoxia-inducible factors, oxidative stress, and ER stress/UPR have been implicated in the pathogenesis of these diseases, highlighting their significance in drug development.