Role of connexin 43 in pulmonary hypertension in mice - 26/03/18
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Résumé |
Introduction |
Expression of connexin 43 (Cx43), protein that forms communicating junctions, is increased in intrapulmonary arteries (IPA) from rats suffering from hypoxic pulmonary hypertension (PH).
Objectives |
In the present study, we compare heterozygous Cx43 knockout mice (Cx43+/−) to their wild type littermate mice (Cx43+/+) in normoxia (N) and chronic hypoxia (CH) in order to further address the role of Cx43 in PH.
Methods |
Experiments were conducted on Cx43+/+ and Cx43+/− CD1 male mice, which were either housed in ambient room air (N) or exposed to CH (0.5atm during 3 weeks) to induce PH. Right ventricular systolic pressure (RVSP) was measured with a catheter. IPA remodelling was estimated by eosin-hematoxylin staining whereas right ventricular hypertrophy was estimated by fulton index (ratio of right ventricle to left ventricle plus septum weight).
Results |
In N, body weight, fulton index and RVSP were similar in Cx43+/− and Cx43+/+. In CH vs. N, body weight was decreased whereas fulton index as well as RVSP were increased in both Cx43+/− and Cx43+/+. In CH, fulton index was slightly smaller in Cx43+/− vs. Cx43+/+. Immunofluorescent labelling of IPA showed that Cx43 was expressed in endothelium as well as smooth muscle in Cx43+/+ whereas it was strongly decreased in Cx43+/−. Quantitative RT-PCR and Western Blot showed a decrease of Cx43 mRNA and proteins respectively, in IPA from both N and CH Cx43+/− whereas Cx37 and Cx40 mRNA were stable. IPA wall thickness was increased in CH vs. N Cx43+/+ but not Cx43+/−. PCNA labelling experiments confirmed the presence of IPA cell proliferation in CH Cx43+/+ and its absence in CH Cx43+/−. With TUNEL methodology, we demonstrated the absence of lung tissue apoptosis. In both CH and N Cx43+/− vs. Cx43+/+, reactivity to endothelin-1 was increased and relaxation to carbachol was unchanged.
Conclusion |
Altogether, Cx43 seems to play an important role in IPA remodelling and reactivity in CH-PH mice.
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Vol 10 - N° 2
P. 248-249 - avril 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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