title: Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium.
abstract: OBJECTIVE
  A distinctive feature of sepsis is a pleiotropic modification of membrane protein expression in the vascular endothelium, associated with diminished endothelium-dependent relaxation (endothelial dysfunction). In cultured endothelial cells, inflammatory stimuli alter expression of connexins (Cx), proteins that make up the gap junctions responsible for intercellular communication. In the present study, we tested whether the polymicrobial sepsis induced by cecal ligation and perforation in the rat alters the expression of the connexins present in the vascular endothelium (i.e., Cx37, Cx40, and Cx43). We also examined a possible association between such changes and endothelial dysfunction in this model.
  
  
  METHODS
  Animal study, with two parallel groups.
  
  
  METHODS
  Animal research facility.
  
  
  METHODS
  One hundred four male adult Wistar rats.
  
  
  METHODS
  Rats underwent either cecal ligation and perforation to induce sepsis or a sham operation and were killed after a variable time, mostly 24 hrs.
  
  
  RESULTS
  Experiments designed to test for the impact of sepsis on connexin expression disclosed a three-fold increase in Cx40 messenger RNA and protein in the aorta, an effect that peaked at 24 hrs after cecal ligation and perforation, was specific to this connexin (i.e., levels of Cx37 and Cx43 did not vary), and was restricted to the aortic endothelium. Experiments designed to test the permeability of interendothelial gap junctions using the scrape-loading method did not show a change in function in the septic group. Finally, a time-course study was designed to test for a possible association of enhanced Cx40 expression with endothelial dysfunction. Endothelium-dependent relaxation was diminished in rings of aorta when harvested from septic rats before (6 hrs after surgery) but not at the time when enhanced Cx40 expression occurred (12 and 24 hrs).
  
  
  CONCLUSIONS
  In this experimental model, recovery from an early transient dysfunction of the aortic endothelium is associated with an enhanced expression of aortic endothelial Cx40.
authors.affiliation: Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rignault
authors.forename: Jacques-Antoine
authors.initials: JA
authors.lastname: Haefliger
authors.forename: Didier
authors.initials: D
authors.lastname: Gasser
authors.forename: Michèle
authors.initials: M
authors.lastname: Markert
authors.forename: Pascal
authors.initials: P
authors.lastname: Nicod
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
authors.forename: Bernard
authors.initials: B
authors.lastname: Waeber
authors.forename: François
authors.initials: F
authors.lastname: Feihl
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000503:physiopathology; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D015999:Multivariate Analysis; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000503:physiopathology*; D015854:Up-Regulation; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein