the epidermal growth factor receptor is involved in angiotensin ii but not aldosteronesalt-induced cardiac remodelling表皮生长因子受体参与了血管紧张素ⅱ但不是aldosteronesalt-induced心脏重塑.pdfVIP

The Epidermal Growth Factor Receptor Is Involved in Angiotensin II But Not Aldosterone/Salt-Induced Cardiac Remodelling Smail Messaoudi1,2., An Di Zhang1,2., Violaine Griol-Charhbili1,2, Brigitte Escoubet1,3,4, Junichi Sadoshima5, Nicolette Farman1,2, Frederic Jaisser1,2* ˆ 1 INSERM, U872, Centre de Recherche des Cordeliers, Paris, France, 2 Pierre et Marie Curie University, Paris VI, Paris, France, 3 Assistance Publique-Hopitaux de Paris, ˆ Hopital Bichat, Paris, France, 4 University Denis Diderot, Paris 7, Paris, France, 5 Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, United States of America Abstract Experimental and clinical studies have shown that aldosterone/mineralocorticoid receptor (MR) activation has deleterious effects in the cardiovascular system; however, the signalling pathways involved in the pathophysiological effects of aldosterone/MR in vivo are not fully understood. Several in vitro studies suggest that Epidermal Growth Factor Receptor (EGFR) plays a role in the cardiovascular effects of aldosterone. This hypothesis remains to be demonstrated in vivo. To investigate this question, we analyzed the molecular and functional consequences of aldosterone exposure in a transgenic mouse model with constitutive cardiomyocyte-specific overexpression of a mutant EGFR acting as a dominant negative protein (DN-EGFR). As previously reported, Angiotensin II-mediated cardiac remodelling was prevented in DN-EGFR mice.