Direct left ventricular wall stretch activates GATA4 binding in perfused rat heart: Involvement of autocrine/paracrine pathways

Nina Hautala, Olli Tenhunen, Istvan Szokodi, Heikki Ruskoaho

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The signaling cascades that activate transcription factors during cardiac hypertrophy are largely unknown. To evaluate the mechanisms for GATA4 and activator protein-1 (AP-1) activation, isolated perfused rat hearts were exposed to elevated wall stretch by inflating a left ventricular balloon. Gel mobility shift assays were used to analyze the transacting factors that interact with the GATA or the AP-1 motifs of the B-type natriuretic peptide (BNP) promoter. Direct wall stretch for 30 min produced a twofold increase (P<0.001) in left ventricular BNP GATA4- but not GATA5- and GATA6-binding activity. In addition, increased BNP AP-1-binding activity and the presence of c-fos were demonstrated in wall-stretch-stimulated ventricles compared with unloaded ventricles. The mixed endothelin-1 ETA/ETB receptor antagonist bosentan and the angiotensin II (Ang II) type 1 (AT1) receptor antagonist CV-11974 completely inhibited the wall-stretch-induced increase in left ventricular BNP GATA4 and AP-1 activity. Infusions of ET-1 and Ang II in the absence of wall stretch also stimulated BNP GATA4-binding activity (P<0.01). These results show that ET-1 and Ang II are required for the stimulation of GATA4 and AP-1 DNA-binding activity in response to direct left ventricular wall stretch.

Original languageEnglish
Pages (from-to)362-369
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume443
Issue number3
DOIs
Publication statusPublished - Feb 5 2002

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Keywords

  • Angiotensin II
  • B-type natriuretic peptide (BNP)
  • Endothelin-1
  • Left ventricle
  • Transcription factors
  • Wall stretch

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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