Cardiac remodeling in Gαq and Gα11 knockout mice. (1st January 2016)

• Record Type: Journal Article
• Authors: Wiesen, Kathrina; Kaiser, Elisabeth; Schröder, Laura; Scholz, Anke; Ruppenthal, Sandra; Reil, Jan-Christian; Backes, Christina; Meese, Eckart; Meier, Carola; Bogdanova, Anna; Lipp, Peter; Kaestner, Lars
• Is Part Of: International journal of cardiology. Volume 202(2016)
• Page Start: 836
• Page End: 845
• Publication Date: 2016-01-01
• Subjects: Gαq/Gα11-signaling -- Cardiac tissue-remodeling -- Matricellular proteins -- Cyr61; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2015.10.069
• Languages: English
• ISSNs: 0167-5273

Abstract

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 and results: 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.