Hypoxia-induced inhibition of mTORC1 activity in the developing lung: a possible mechanism for the developmental programming of pulmonary hypertension.

Hypoxia-induced inhibition of mTORC1 activity in the developing lung: a possible mechanism for the developmental programming of pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2021 Jan 08;: Authors: Mundo W, Wolfson G, Moore LG, Houck JA, Park D, Julian CG Abstract Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Pregnant C57/BL6 dams were placed in hyperbaric (760 mmHg) or hypobaric chambers during gestation (505 mmHg, day 15 through postnatal day 4) or adulthood (420 mmHg, postnatal day 21 through 8wks). Pulmonary hemodynamics and right ventricular systolic pressure (RVSP) were measured at 8wks. mTOR pathway proteins were assessed in fetal (day 18.5) and adult lung (8wks). Perinatal hypoxia induced PH during adulthood, even in the absence of a sustained secondary hypoxic exposure, as indicated by reduced pulmonary artery acceleration time (PAAT) and peak flow velocity through the pulmonary valve, as well as greater RVSP, RV wall thickness and RV/LV weight. Such effects were independent of increased blood viscosity. In fetal lung homogenates, hypoxia reduced the expression...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research