Fessel 2013 Am J Respir Cell Mol Biol

Fessel JP, Flynn CR, Robinson LJ, Penner NL, Gladson S, Kang C, Wasserman DH, Hemnes AR, West JD (2013) Hyperoxia synergizes with mutant BMPR2 to cause metabolic stress, oxidant injury, and pulmonary hypertension. Am J Respir Cell Mol Biol 49: 778-787.

» PMID: 23742019

Fessel JP, Flynn CR, Robinson LJ, Penner NL, Gladson S, Kang C, Wasserman DH, Hemnes AR, West JD (2013) Am J Respir Cell Mol Biol

Abstract: Pulmonary arterial hypertension (PAH) has been associated with a number of different but interrelated pathogenic mechanisms. Metabolic and oxidative stresses have been shown to play important pathogenic roles in a variety of model systems. However, many of these relationships remain at the level of association. We sought to establish a direct role for metabolic stress and oxidant injury in the pathogenesis of PAH. Mice that universally express a disease-causing Bmpr2 mutation were exposed to room air or to brief daily hyperoxia (95% oxygen for 3 hours) for 6 weeks and compared to wild-type animals with identical exposures. In both murine tissues and cultured endothelial cells, expression of mutant Bmpr2 was sufficient to cause oxidant injury that was particularly pronounced in mitochondrial membranes. With enhancement of mitochondrial generation of reactive oxygen species by hyperoxia, oxidant injury was substantially enhanced in mitochondrial membranes, even in tissues distant from the lung. Hyperoxia, despite its vasodilatory actions in the pulmonary circulation, significantly worsened the PAH phenotype (elevated RVSP, decreased cardiac output, increased pulmonary vascular occlusion) in Bmpr2 mutant animals. These studies demonstrate that oxidant injury and metabolic stress contribute directly to disease development and provide further evidence for PAH as a systemic disease with life-limiting cardiopulmonary manifestations. • Keywords: Pulmonary arterial hypertension, Bmpr2, hyperoxia

• O2k-Network Lab: US TN Nashville Fessel JP, US TN Nashville Wasserman DH

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Mouse  Tissue;cell: Heart, Lung;gill, Endothelial; Epithelial; Mesothelial Cell"Endothelial; Epithelial; Mesothelial Cell" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.  Preparation: Intact cells 

Regulation: O2"O2" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 

HRR: Oxygraph-2k 

Labels