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An angiotensin II- and NF-κB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension

Alonso, Florian ; Krattinger, Nathalie ; Mazzolai, Lucia ; Simon, Alexander ; Waeber, Gérard ; Meda, Paolo ; Haefliger, Jacques-Antoine

In: Cardiovascular Research, 2010, vol. 87, no. 1, p. 166-176

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    Titre
    • An angiotensin II- and NF-κB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension
    Auteur
    • Alonso, Florian. Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, University Hospital, CHUV-1011 Lausanne, Switzerland
    • Krattinger, Nathalie. Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, University Hospital, CHUV-1011 Lausanne, Switzerland
    • Mazzolai, Lucia. Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, University Hospital, CHUV-1011 Lausanne, Switzerland
    • Simon, Alexander. Department of Physiology, College of Medicine, University of Arizona, Tucson, AZ, USA
    • Waeber, Gérard. Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, University Hospital, CHUV-1011 Lausanne, Switzerland
    • Meda, Paolo. Department of Cell Physiology and Metabolism, University of Geneva, School of Medicine, CMU, 1211 Genève 4, Switzerland
    • Haefliger, Jacques-Antoine. Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, University Hospital, CHUV-1011 Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Cardiovascular Research, 2010, vol. 87, no. 1, p. 166-176. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:297793
    Summary
    Aims Connexins (Cxs) play a role in the contractility of the aorta wall. We investigated how connexins of the endothelial cells (ECs; Cx37, Cx40) and smooth muscle cells (SMCs; Cx43, Cx45) of the aorta change during renin-dependent and -independent hypertension. Methods and results We subjected both wild-type (WT) mice and mice lacking Cx40 (Cx40−/−), to either a two-kidney, one-clip procedure or to N-nitro-l-arginine-methyl-ester treatment, which induce renin-dependent and -independent hypertension, respectively. All hypertensive mice featured a thickened aortic wall, increased levels of Cx37 and Cx45 in SMC, and of Cx40 in EC (except in Cx40−/− mice). Cx43 was up-regulated, with no effect on its S368 phosphorylation, only in the SMCs of renin-dependent models of hypertension. Blockade of the renin-angiotensin system of Cx40−/− mice normalized blood pressure and prevented both aortic thickening and Cx alterations. Ex vivo exposure of WT aortas, carotids, and mesenteric arteries to physiologically relevant levels of angiotensin II (AngII) increased the levels of Cx43, but not of other Cx. In the aortic SMC line of A7r5 cells, AngII activated kinase-dependent pathways and induced binding of the nuclear factor-kappa B (NF-κB) to the Cx43 gene promoter, increasing Cx43 expression. Conclusion In both large and small arteries, hypertension differently regulates Cx expression in SMC and EC layers. Cx43 is selectively increased in renin-dependent hypertension via an AngII activation of the extracellular signal-regulated kinase and NF-κB pathways