title: Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.
abstract: Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.
authors.affiliation: Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140; email: seguchi@temple.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Forrester
authors.affiliation: Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140; email: seguchi@temple.edu.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawai
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Shannon
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Walter
authors.initials: W
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
authors.affiliation: Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140; email: seguchi@temple.edu.
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D066246:ErbB Receptors
keywords: aldosterone; angiotensin II; endothelium; heart; kidney; signal transduction; vascular smooth muscle