title: Angiotensin II type1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload.
abstract: Hypertrophy of mammalian cardiac muscle is mediated, in part, by angiotensin II through an angiotensin II type1a receptor (AT1aR)-dependent mechanism. To understand how the level of AT1aRs is altered in this pathological state, we studied the expression of an injected AT1aR promoter-luciferase reporter gene in adult rat hearts subjected to an acute pressure overload by aortic coarctation. This model was validated by demonstrating that coarctation increased expression of the alpha-skeletal actin promoter 1.7-fold whereas the alpha-myosin heavy chain promoter was unaffected. Pressure overload increased expression from the AT1aR promoter by 1. 6-fold compared with controls. Mutations introduced into consensus binding sites for AP-1 or GATA transcription factors abolished the pressure overload response but had no effect on AT1aR promoter activity in control animals. In extracts from coarcted hearts, but not from control hearts, a Fos-JunB-JunD complex and GATA-4 were detected in association with the AP-1 and GATA sites, respectively. These results establish that the AT1aR promoter is active in cardiac muscle and its expression is induced by pressure overload, and suggest that this response is mediated, in part, by a functional interaction between AP-1 and GATA-4 transcription factors.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Herzig
authors.forename: S M
authors.initials: SM
authors.lastname: Jobe
authors.forename: H
authors.initials: H
authors.lastname: Aoki
authors.forename: J D
authors.initials: JD
authors.lastname: Molkentin
authors.forename: A W
authors.initials: AW
authors.lastname: Cowley
authors.forename: S
authors.initials: S
authors.lastname: Izumo
authors.forename: B E
authors.initials: BE
authors.lastname: Markham
mesh_terms: D000818:Animals; D001017:Aortic Coarctation; D001665:Binding Sites / Q000235:genetics; D001794:Blood Pressure; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011945:Receptors, Angiotensin; D018808:Transcription Factor AP-1; D014157:Transcription Factors