title: Early genetic responses in rat vascular tissue after simulated diving.
abstract: Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats (n = 8) and unexposed controls (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po(2) instigated the observed genetic reactions.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. Ingrid.Eftedal@ntnu.no
authors.forename: Ingrid
authors.initials: I
authors.lastname: Eftedal
authors.forename: Arve
authors.initials: A
authors.lastname: Jørgensen
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Røsbjørgen
authors.forename: Arnar
authors.initials: A
authors.lastname: Flatberg
authors.forename: Alf O
authors.initials: AO
authors.lastname: Brubakk
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D016000:Cluster Analysis; D004242:Diving / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010100:Oxygen