P66shc deficient mice develope decreased right heart hypertrophy via a Cyclophilin D dependent mechanism in hypoxia-induced pulmonary hypertension

In acute and chronic hypoxia the response of the pulmonary vasculature is suggested to be regulated via mitochondrial reactive oxygen species (ROS). In response to cellular stress the mitochondrial regulator protein p66shc enhances the ROS-production probably via the pro-apoptotic protein cyclophilin D (CypD). We hypothesized in p66shc-deficient mice lower hypoxic pulmonary vasoconstriction (HPV) and pulmonary hypertension (PH) related to lower hypoxia-induced ROS-production. HPV was determined in isolated lungs of p66shc and CypD deficient mice, as well as in mice lacking both proteins, and compared to lungs of…