Cardiac remodeling in Gαq and Gα11 knockout mice.
Int J Cardiol
; 202: 836-45, 2016 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-26476043
ABSTRACT
BACKGROUND:
Although both Gαq- and Gα11-protein signaling are believed to be involved in the regulation of cardiac hypertrophy, their detailed contribution to myocardial function remains elusive. METHODS ANDRESULTS:
We studied remodeling processes in healthy transgenic mice with genetically altered Gαq/Gα11-expression, in particular a global Gα11-knockout and a novel inducible cardiac specific Gαq-knockout, as well as a combined double knockout (dKO) mouse line. Echocardiography and telemetric ECG recordings revealed that compared with wild type mice, hearts of dKO mice showed an increased ejection fraction and a decreased heart rate, irrespective of age resulting in a maintained cardiac output. We attributed these findings to the lack of Gα11, which the absence was associated with a decreased afterload. Histological analysis of the extracellular matrix in the heart depicted a diminished presence of collagen in aging hearts of dKO mice compared to wild-type mice. The results of a transcriptome analysis on isolated ventricular cardiac myocytes revealed alterations of the activity of genes involved in the Gαq/Gα11-dependent regulation of the extracellular matrix, such as the matricellular protein Cyr61.CONCLUSIONS:
From our data we conclude that Gαq/Gα11 signaling pathways play a pivotal role in maintaining gene activity patterns. For the heart we revealed their importance in modulating the properties of the extracellular matrix, a mechanism that might be an important contributor and mechanistic basis for the development of pressure-overload induced cardiac hypertrophy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Cardiomegalia
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Remodelação Ventricular
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Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
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Frequência Cardíaca
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article