title: Reversible heart failure in G alpha(q) transgenic mice.
abstract: For many patients with cardiac insufficiency, the disease progresses inexorably to organ dilatation, pump failure, and death. Although there are examples of reversible heart failure in man, our understanding of how the myocardium repairs itself is limited. A well defined animal model of reversible heart failure would allow us to better investigate these restorative processes. Receptors that activate Galpha(q), a signal transduction molecule in the heterotrimeric G protein superfamily, are thought to play a key role in the development of heart failure. We demonstrated previously that mice expressing a recombinant Galpha(q) protein, the activity of which can be turned on or off at will in cardiac myocytes, develop a dilated cardiomyopathy with generalized edema and heart failure following activation of the protein (Fan, G., Jiang, Y.-P., Lu, Z., Martin, D. W., Kelly, D. J., Zuckerman, J. M., Ballou, L. M., Cohen, I. S., and Lin, R. Z. (2005) J. Biol. Chem. 280, 40337-40346). Here we report that the contractile dysfunction and pathological structural changes in the myocardium improved significantly after termination of the Galpha(q) signal, even in animals with overt heart failure. Abnormalities in two proteins that regulate Ca(2+) handling in myocytes, phospholamban and the voltage-dependent L-type Ca(2+) channel, were also reversed, as was the increased expression of genes that are associated with heart failure. These results indicate that the heart has a substantial reparative capacity if the molecular signals responsible for the myocardial dysfunction can be identified and blocked.
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Jiang
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ballou
authors.forename: Zhongju
authors.initials: Z
authors.lastname: Lu
authors.lastname: Li Wan
authors.forename: Damon J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Ira S
authors.initials: IS
authors.lastname: Cohen
authors.forename: Richard Z
authors.initials: RZ
authors.lastname: Lin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism
chemical_list: D043802:GTP-Binding Protein alpha Subunits, Gq-G11