Faculty Collaboration Database

Angiotensin II type1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload. Proc Natl Acad Sci U S A 1997 Jul 08;94(14):7543-8

Date

07/08/1997

Pubmed ID

9207128

Pubmed Central ID

PMC23858

DOI

10.1073/pnas.94.14.7543

Scopus ID

2-s2.0-0030612599 (requires institutional sign-in at Scopus site)   180 Citations

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.

Author List

Herzig TC, Jobe SM, Aoki H, Molkentin JD, Cowley AW Jr, Izumo S, Markham BE

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Aortic Coarctation
Binding Sites
Blood Pressure
Cells, Cultured
DNA-Binding Proteins
Erythroid-Specific DNA-Binding Factors
Gene Expression Regulation
Gene Transfer Techniques
Heart
Male
Mutation
Myocardium
Rats
Rats, Sprague-Dawley
Rats, Wistar
Receptors, Angiotensin
Transcription Factor AP-1
Transcription Factors