Kressig 2013 Abstract IOC79
|Kressig F (2013) et al. Mechanism of increased pulmonary vascular remodeling in UCP2 k/o mice. Mitochondr Physiol Network 18.07|
Increased pulmonary vascular remodeling is a hallmark of pulmonary hypertension (PH), a severe disease of the pulmonary vasculature that can be induced by exposure to chronic hypoxia. In mice deficient of the uncoupling protein 2 (UCP2 k/o) pulmonary vascular remodeling is increased, as well as proliferation of pulmonary arterial smooth muscle cells (PASMC). We thus determined mitochondrial function in PASMC of UCP2 k/o mice and WT mice after exposure to hypoxia to investigate the role of mitochondria in these processes. Respiration and mitochondrial membrane potential (MMP) of PASMC isolated from UCP2 k/o and WT mice were measured under baseline conditions and after exposure to hypoxia by high resolution respirometry in combination with the fluorescent probe safranine. MMP was additionally measured in intact PASMC by fluorescence microscopy with JC-1. Reactive oxygen species (ROS) were determined by the fluorescent dye HyPerCyto. Mitochondrial respiration was decreased in PASMC of both mouse strains after exposure to hypoxia (48 h, 1% oxygen), but unchanged in PASMC of UCP2 k/o mice compared to WT mice. MMP was increased in PASMC after exposure to hypoxia compared to normoxic PASMC, as well as in PASMC of UCP2 k/o compared to WT PASMC in normoxia. Concentration of cellular ROS was also increased in PASMC of UCP2 k/o compared to WT PASMC in normoxia. Increased proliferation of PASMC of UCP2 k/o mice could be inhibited by ROS inhibitors. An increase in MMP may lead via increased ROS to increased PASMC proliferation in UCP2 k/o mice. The exact mechanism for the increase of MMP in PASMC of UCP2 k/o and hypoxic PASMC of WT mice remains to be elucidated.
• Keywords: pulmonary hypertension(ph), chronic hypoxia, pulmonary vascular remodeling, UCP2k/o, disease model, PASMC, mmp
• O2k-Network Lab: DE Giessen Weissmann N
Labels: MiParea: Respiration, mt-Membrane, Genetic knockout;overexpression Pathology: Other Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Lung;gill, Other cell lines Preparation: Permeabilized cells, Isolated mitochondria Enzyme: Uncoupling protein Regulation: ADP, Calcium, Coupling efficiency;uncoupling, Flux control, Inhibitor, mt-Membrane potential, Substrate, Uncoupler Coupling state: LEAK
HRR: Oxygraph-2k, O2k-Fluorometer
Excellence Cluster Cardio-Pulmonary System (ECCPS), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center for Lung Research (DZL). Justus-Liebig-University, Giessen, Germany