標題: Membrane translocation of small GTPase Rac1 and activation of STAT1 and STAT3 in pacing-induced sustained atrial fibrillation
作者: Tsai, Chia-Ti
Lin, Jiunn-Lee
Lai, Ling-Ping
Lin, Chih-Sheng
Huang, Sheoi K. Stephen
生物科技學系
Department of Biological Science and Technology
關鍵字: atrial fibrillation;angiotensin II;mitogen-activated protein kinase;Janus kinase/signal transducers and activators of transcription;small GTPase;Rac1
公開日期: 1-Sep-2008
摘要: 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 interteukin-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.
URI: http://dx.doi.org/10.1016/j.hrthm.2008.05.012
http://hdl.handle.net/11536/8394
ISSN: 1547-5271
DOI: 10.1016/j.hrthm.2008.05.012
期刊: HEART RHYTHM
Volume: 5
Issue: 9
起始頁: 1285
結束頁: 1293
Appears in Collections:Articles