Inhaltspezifische Aktionen

A06

Sensing and signaling events underlying development and recovery of hypoxia-induced pulmonary hypertension

Local acute alveolar hypoxia induces hypoxic pulmonary vasoconstriction (HPV) to optimize gas exchange, while generalized chronic hypoxia causes lung vascular remodeling and pulmonary hypertension (PH). We delineated the role of reactive oxygen species originating from mitochondria and NADPH-oxidases in both processes, identified a new key regulator of the mitochondrial oxygen sensing mechanism underlying HPV and identified novel targets of hypoxia-induced PH. We now aim 1) to further uncover the molecular mechanisms of acute mitochondrial oxygen sensing, 2) to transfer mitochondrial mechanisms from cancer to hypoxia-induced and multifactorial PH, and 3) to test the relevance of the newly identified targets for treatment of disturbed HPV and PH.