Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium


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Article: article d'un périodique ou d'un magazine.
Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium
Critical Care Medicine
Rignault  S., Haefliger  J. A., Gasser  D., Markert  M., Nicod  P., Liaudet  L., Waeber  B., Feihl  F.
0090-3493 (Print)
Statut éditorial
Date de publication
Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun
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. DESIGN: Animal study, with two parallel groups. SETTING: Animal research facility. SUBJECTS: One hundred four male adult Wistar rats. INTERVENTIONS: Rats underwent either cecal ligation and perforation to induce sepsis or a sham operation and were killed after a variable time, mostly 24 hrs. MEASUREMENTS AND MAIN 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). CONCLUSION: In this experimental model, recovery from an early transient dysfunction of the aortic endothelium is associated with an enhanced expression of aortic endothelial Cx40.
Animals Aorta/*metabolism/physiopathology Connexin 43/metabolism Connexins/*metabolism Endothelium, Vascular/*metabolism/physiopathology Male Multivariate Analysis Rats Rats, Wistar Sepsis/*physiopathology Up-Regulation
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Création de la notice
25/01/2008 13:47
Dernière modification de la notice
20/08/2019 13:29
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