Cardiac Effects of Attenuating Gs[alpha] - Dependent Signaling

Inhibition of [beta]-adrenergic signalling plays a key role in treatment of heart failure. Gs[alpha] is essential for [beta]-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing [beta]-adrenergic signalling in the heart at the level of Gs[alpha] i...

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Bibliographic Details
Published in:PloS one 2016-01, Vol.11 (1)
Main Authors: Streit, Marcus R, Weiss, Celine S, Meyer, Sören, Ochs, Marco M, Hagenmueller, Marco, Riffel, Johannes H, Buss, Sebastian J, Heger, Thomas, Katus, Hugo A, Hardt, Stefan E
Format: Article
Language:English
Subjects:
Analysis
Care and treatment
Cellular signal transduction
Genetic aspects
Heart failure
Physiological aspects
Online Access:Get full text
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Summary:Inhibition of [beta]-adrenergic signalling plays a key role in treatment of heart failure. Gs[alpha] is essential for [beta]-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing [beta]-adrenergic signalling in the heart at the level of Gs[alpha] is a promising option. We analyzed the influence of Gs[alpha] on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice) overexpressing a dominant negative Gs[alpha]-mutant under control of the [alpha]-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic [beta]-adrenergic stimulation. At rest, Gs[alpha]-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0146988