Abstract 12465: Short-term Rapid Atrial Pacing Promotes Gene Expression of Prothrombotic Molecules in the Liver - Cardio-hepatic Interaction in Atrial Fibrillation
Introduction: Atrial fibrillation (AF) is known to activate intrinsic coagulation system leading to hypercoagulation of the blood. The liver is considered as the major source of coagulation factors and other prothrombotic molecules. However, it is still unknown whether rapid atrial excitation affects gene expression remotely in the liver.
Methods and Results: The AF model was created by rapid atrial pacing at the frequency of 1200 bpm in anesthetized 10-week-old Sprague-Dawley rats. The livers were collected and analyzed after the pacing of 4, 8 and 12 hours. Sham-operated rats underwent the identical procedure without electrical stimulation. No significant differences of blood pressure or heart rate were observed among groups. The quantitative RT-PCR revealed that rapid atrial pacing of 12 hours significantly augmented the hepatic mRNA expressions of fibrinogen α-chain (225%), β-chain (287%), γ-chain (240%), plasminogen activator inhibitor-1 (PAI-1, 509%), prothrombin (177%), antithrombin-III (152%) and plasminogen (149%). The time course analysis for fibrinogen α, β, γ-chain and PAI-1 showed that these expressions were progressively increased in the liver by rapid atrial pacing, being statistically significant at 8 or 12 hours (Figure). In addition, the hepatic proteins of fibrinogen and PAI-1 quantified by Western blotting were also enhanced by 12-hour atrial pacing (309% and 275%, respectively).
Conclusion: Even the short-term rapid atrial excitation mimicking paroxysmal AF promoted the hepatic gene expressions of prothrombotic molecules including fibrinogen, prothrombin, antithrombin-III, plasminogen and PAI-1. These findings might imply the cardio-hepatic interaction in AF and provide new insight into the prevention of AF-associated thromboembolism.
- © 2013 by American Heart Association, Inc.