rwj-56110 and Atrial-Fibrillation

Atrial fibrillation (AF) produces a hypercoagulable state. Stimulation of protease-activated receptors by coagulation factors provokes pro-fibrotic, pro-hypertrophic, and pro-inflammatory responses in a variety of tissues. We studied the effects of thrombin on atrial fibroblasts and tested the hypothesis that hypercoagulability contributes to the development of a substrate for AF.. In isolated rat atrial fibroblasts, thrombin enhanced the phosphorylation of the pro-fibrotic signalling molecules Akt and Erk and increased the expression of transforming growth factor β1 (2.7-fold) and the pro-inflammatory factor monocyte chemoattractant protein-1 (6.1-fold). Thrombin also increased the incorporation of. The hypercoagulable state during AF causes pro-fibrotic and pro-inflammatory responses in adult atrial fibroblasts. Hypercoagulability promotes the development of a substrate for AF in transgenic mice and in goats with persistent AF. In AF goats, nadroparin attenuates atrial fibrosis and the complexity of the AF substrate. Inhibition of coagulation may not only prevent strokes but also inhibit the development of a substrate for AF.

Topics: Analysis of Variance; Animals; Antithrombins; Atrial Fibrillation; Cell Proliferation; Dabigatran; Female; Fibrinolytic Agents; Fibroblasts; Fibrosis; Goats; Heart Atria; Indazoles; Mice, Transgenic; Nadroparin; Peptide Hydrolases; Pyrroles; Quinazolines; Rats; Receptors, Thrombin; Thrombin; Thrombophilia; Urea