Marked enhancement in myocardial function resulting from overexpression of a human beta-adrenergic receptor gene.
Transgenic mice with intense cardiac expression of a human beta-adrenergic receptor gene were engineered and shown to display marked improvements in baseline myocardial and left ventricular function. Heart/body weight ratios and histologic appearance were not found to be significantly altered, suggesting that receptor gene expression did not induce pathologic changes. Given the substantial reduction in beta-adrenergic receptor density and resultant reduction in inotropic responsiveness observed in chronic heart failure, these findings represent a novel approach for increasing myocardial function with important clinical implications.
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710.
C A
CA
Milano
L F
LF
Allen
P C
PC
Dolber
T D
TD
Johnson
H A
HA
Rockman
R A
RA
Bond
R J
RJ
Lefkowitz
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D001835:Body Weight; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006321:Heart / Q000033:anatomy & histology; D006333:Heart Failure / Q000628:therapy; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics; D009929:Organ Size; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000502:physiology; D016277:Ventricular Function, Left / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; D009320:Atrial Natriuretic Factor; D009218:Myosins