title: Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor.
abstract: Transgenic mice were created with cardiac-specific overexpression of the beta 2-adrenergic receptor. This resulted in increased basal myocardial adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo; these parameters at baseline in the transgenic animals were equal to those observed in control animals maximally stimulated with isoproterenol. These results illustrate a useful approach for studying the effect of gene expression on cardiac contractility. Because chronic heart failure in humans is accompanied by a reduction in the number of myocardial beta-adrenergic receptors and in inotropic responsiveness, these results suggest a potential gene therapy approach to this disease state.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710.
authors.forename: C A
authors.initials: CA
authors.lastname: Milano
authors.forename: L F
authors.initials: LF
authors.lastname: Allen
authors.forename: H A
authors.initials: HA
authors.lastname: Rockman
authors.forename: P C
authors.initials: PC
authors.lastname: Dolber
authors.forename: T R
authors.initials: TR
authors.lastname: McMinn
authors.forename: K R
authors.initials: KR
authors.lastname: Chien
authors.forename: T D
authors.initials: TD
authors.lastname: Johnson
authors.forename: R A
authors.initials: RA
authors.lastname: Bond
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy; D006339:Heart Rate; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D016277:Ventricular Function, Left
chemical_list: D011943:Receptors, Adrenergic, beta; D009218:Myosins; D000262:Adenylyl Cyclases; D007545:Isoproterenol