Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast activity

Jansen, John A.
van Veen, Toon A. B.
de Jong, Sanne
van der Nagel, Roel
van Stuijvenberg, Leonie
Driessen, Helen
Labzowski, Ronald
Oefner, Carolin M.
Bosch, Astrid A.
Nguyen, Tri Q.
Goldschmeding, Roel
Vos, Marc A.
de Bakker, Jacques M. T.
van Rijen, Harold V. M.

Open link

Publication date

January 2012

DOI

10.1161/circep.111.966580

Publisher

Ovid Technologies (Wolters Kluwer Health)

ISSN

1941-3149

Abstract

Arrhythmogenic ventricular remodeling is hallmarked by both reduced gap junction expression and increased collagen deposition. We hypothesized that reduced connexin43 (Cx43) expression is responsible for enhanced fibrosis in the remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we investigated the effect of normal or reduced Cx43 expression on the formation of fibrosis in a physiological (aging) and pathophysiological (transverse aortic constriction [TAC]) mouse model. The Cx43(fl/fl) and Cx43(CreER(T)/fl) mice were aged 18 to 21 months or, at the age of 3 months, either TAC or sham operated and euthanized after 16 weeks. Epicardial activation mapping of the right and left ventricles was performed on Langendorff perfused...