title: Cardiac remodeling in Gαq and Gα11 knockout mice.
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.
  
  
  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.
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty and the Zürich Center for Integrative Human Physiology, University of Zürich, 8057 Zürich, Switzerland; Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Kathrina
authors.initials: K
authors.lastname: Wiesen
authors.affiliation: Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kaiser
authors.affiliation: Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Schröder
authors.affiliation: Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Scholz
authors.affiliation: Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruppenthal
authors.affiliation: Clinic for Internal Medicine III, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Reil
authors.affiliation: Institute for Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Institute for Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.affiliation: Anatomy, Saarland University, 66421 Homburg/Saar, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Meier
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty and the Zürich Center for Integrative Human Physiology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bogdanova
authors.affiliation: Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany. Electronic address: peter.lipp@uks.eu.
authors.forename: Peter
authors.initials: P
authors.lastname: Lipp
authors.affiliation: Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, 66421 Homburg/Saar, Germany. Electronic address: lars_kaestner@me.com.
authors.forename: Lars
authors.initials: L
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000172:deficiency* / Q000235:genetics; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Cardiac tissue-remodeling; Cyr61; Gα(q)/Gα(11)-signaling; Matricellular proteins