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


CONCLUSIONS
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.
Tsai
Chia-Ti
CT
Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. fang31@ms39.hinet.net
Lin
Jiunn-Lee
JL
Lai
Ling-Ping
LP
Lin
Chih-Sheng
CS
Huang
Sheoi K Stephen
SK
D000804:Angiotensin II / Q000235:genetics; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics*; D002304:Cardiac Pacing, Artificial; D022082:Cellular Structures; D005109:Extracellular Matrix / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics*; D053614:Janus Kinase 2 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D023421:Models, Animal; D050794:STAT1 Transcription Factor / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction; D013552:Swine; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D000804:Angiotensin II; D053614:Janus Kinase 2; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; D020830:rac1 GTP-Binding Protein