Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor.
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.
Milano
C A
CA
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Allen
L F
LF
Rockman
H A
HA
Dolber
P C
PC
McMinn
T R
TR
Chien
K R
KR
Johnson
T D
TD
Bond
R A
RA
Lefkowitz
R J
RJ
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
D011943:Receptors, Adrenergic, beta; D009218:Myosins; D000262:Adenylyl Cyclases; D007545:Isoproterenol