semaxinib and Mitochondrial-Diseases

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that leads to right ventricular failure. Skeletal muscle maladaptations limit physical activity and may contribute to disease progression. The role of alarmin/inflammatory signaling in PAH respiratory muscle dysfunction is unknown. We hypothesized that diaphragm mitochondrial and contractile functions are impaired in SU5416/hypoxia-induced pulmonary hypertension due to increased systemic IL-33 signaling. We induced pulmonary hypertension in adult C57Bl/6 J (WT) and ST2 (IL1RL1) gene ablated mice by SU5416/hypoxia (SuHx). We measured diaphragm fiber mitochondrial respiration, inflammatory markers, and contractile function ex vivo. SuHx reduced coupled and uncoupled permeabilized myofiber respiration by ∼40 %. During coupled respiration with complex I substrates, ST2

Topics: Animals; Diaphragm; Disease Models, Animal; Hypertension, Pulmonary; Hypoxia; Indoles; Interleukin-1 Receptor-Like 1 Protein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Mitochondrial Diseases; Muscle Contraction; Protein Kinase Inhibitors; Pulmonary Arterial Hypertension; Pyrroles