G protein, phosphorylated-GATA4 and VEGF expression in the hearts of transgenic mice overexpressing β1- and β2-adrenergic receptors

Mol Med Rep. 2017 Jun;15(6):4049-4054. doi: 10.3892/mmr.2017.6526. Epub 2017 Apr 28.

Abstract

β1- and β2-adrenergic receptors (ARs) regulate cardiac contractility, calcium handling and protein phosphorylation. The present study aimed to examine the expression levels of vascular endothelial growth factor A (VEGF‑A) and several G proteins, and the phosphorylation of transcription factor GATA binding protein 4 (GATA4), by western blot analysis, using isolated hearts from 6 month‑old transgenic (TG) mice that overexpress β1AR or β2AR. Cardiac contractility/relaxation and heart rate was increased in both β1AR TG and β2AR TG mouse hearts compared with wild type; however, no significant differences were observed between the β1‑ and β2AR TG mouse hearts. Protein expression levels of inhibitory guanine nucleotide‑binding protein (Gi) 2, Gi3 and G‑protein‑coupled receptor kinase 2 were upregulated in both TG mice, although the upregulation of Gi2 was more prominent in the β2AR TG mice. VEGF‑A expression levels were also increased in both TG mice, and were highest in the β1AR TG mice. In addition, the levels of phosphorylated‑GATA4 expression were increased in β1‑ and β2AR TG mice. In conclusion, the present study demonstrated that cardiac contractility/relaxation and heart rate is increased in β1AR TG and β2AR TG mice, and indicated that this increase may be related to the overexpression of G proteins and G‑protein‑associated proteins.

MeSH terms

  • Animals
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Cardiomegaly / physiopathology
  • GATA4 Transcription Factor / genetics*
  • GATA4 Transcription Factor / metabolism
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Gene Expression*
  • Heart / physiology
  • Heart / physiopathology
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism*
  • Receptors, Adrenergic, beta-1 / genetics*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • GATA4 Transcription Factor
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Vascular Endothelial Growth Factor A
  • GTP-Binding Proteins