Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy.
Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to Gq class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to Gq.
Akhter
S A
SA
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Luttrell
L M
LM
Rockman
H A
HA
Iaccarino
G
G
Lefkowitz
R J
RJ
Koch
W J
WJ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D019556:COS Cells; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018390:Gene Targeting; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000517:prevention & control; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D019076:Transgenes; D017725:Ventricular Pressure
D004075:Diglycerides; D007295:Inositol Phosphates; D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D019950:Mitogen-Activated Protein Kinase 1; D019204:GTP-Binding Proteins