title: Cardiomyopathy induced by cardiac Gs alpha overexpression.
abstract: The goal of this study was to determine whether chronic endogenous sympathetic stimulation resulting from the overexpression of cardiac stimulatory G protein alpha subunit (Gs alpha) in transgenic mice (15.3 +/- 0.1 mo old) resulted in a clinical picture of cardiomyopathy. The left ventricular ejection fraction, measured by echocardiography, was reduced in older mice with Gs alpha overexpression (50.4 +/- 5.4%) compared with age-matched control mice (70.9 +/- 1.6%; P < 0.05). When ejection fractions were compared at similar heart rates, the Gs alpha mice exhibited a greater left ventricular end-diastolic dimension than control mice (4.3 +/- 0.2 vs. 3.7 +/- 0.1 mm; P < 0.05). Baseline heart rates were elevated in conscious Gs alpha mice (722 +/- 27 beats/min; n = 5) compared with control mice (656 +/- 28 beats/min; n = 5). Moreover, electrocardiographic monitoring demonstrated a high incidence of arrhythmias. Increased mortality compared with control mice (31.6 vs. 3.0%; P < 0.01) was also observed. Thus older mice with Gs alpha overexpression exhibit many of the features of dilated cardiomyopathy. This study supports the concept that chronic sympathetic stimulation over an extended period of time, i.e., over the life of an animal, is deleterious and actually may result in cardiomyopathy.
authors.affiliation: Department of Medicine, Harvard Medical School, Massachusetts, USA.
authors.forename: M
authors.initials: M
authors.lastname: Iwase
authors.forename: M
authors.initials: M
authors.lastname: Uechi
authors.forename: D E
authors.initials: DE
authors.lastname: Vatner
authors.forename: K
authors.initials: K
authors.lastname: Asai
authors.forename: R P
authors.initials: RP
authors.lastname: Shannon
authors.forename: R K
authors.initials: RK
authors.lastname: Kudej
authors.forename: T E
authors.initials: TE
authors.lastname: Wagner
authors.forename: D C
authors.initials: DC
authors.lastname: Wight
authors.forename: T A
authors.initials: TA
authors.lastname: Patrick
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: C J
authors.initials: CJ
authors.lastname: Homcy
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics; D009202:Cardiomyopathies / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006339:Heart Rate; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D016277:Ventricular Function, Left
chemical_list: D019204:GTP-Binding Proteins