Membrane translocation of small GTPase Rac1 and activation of STAT1 and STAT3 in pacing-induced sustained atrial fibrillation

Chia Ti Tsai, Jiunn Lee Lin, Ling Ping Lai, Chih Sheng Lin, Sheoi K Stephen Huang

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Angiotensin II and its downstream mitogen-activated protein kinase signaling pathways are involved in the pathogenesis of AF. Pro-inflammatory JAK/STAT is another downstream signaling pathway of Angiotensin II, and its status in AF remains unknown. Objective: The aim of this study was to characterize the status of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways in pacing-induced sustained atrial fibrillation (AF). Methods: AF was induced by atrial pacing at 600/min in 10 adult pigs (AF group), while 10 sham-operated pigs served as the control group. Results: Significant structural and inflammatory changes were noted in the AF group. Atrial tissue angiotensin II level was elevated and STAT1 and STAT3 were activated in the AF group. Nuclear translocation of activated STAT3 and binding to STAT3 consensus DNA sequence were also increased in the AF group. Rac1, the molecular target of statin, which mediates the activation of STAT3 by angiotensin II, was also activated in the AF group. The tissue levels of interleukin-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1), which are known to activate STATs through membrane gp130 and JAKs, were not increased in the AF group. Membrane gp130 and JAKs were also not activated in the AF group. Conclusion: Activated angiotensin II/Rac1/STAT may be associated with or perhaps contribute to the structural and inflammatory changes in pacing-induced sustained trial fibrillation. It may further imply the therapeutic option of combination of angiotensin receptor blocker and statin.

Original languageEnglish
Pages (from-to)1285-1293
Number of pages9
JournalHeart Rhythm
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 1 2008
Externally publishedYes

Keywords

  • Angiotensin II
  • Atrial fibrillation
  • Janus kinase/signal transducers and activators of transcription
  • Mitogen-activated protein kinase
  • Rac1
  • Small GTPase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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