4246 Hypercoagulability promotes atrial fibrosis and fibrillation
| Autor: | Ulrich Schotten, Sander Verheule, Anne-Margreet De Jong, Hetty De Boer, Alexander Maass, Lau, Dennis H., Michiel Rienstra, Pieter Kamphuisen, Hugo Ten Cate, Crijns, Harry J. G., Isabelle Van Gelder, Zonneveld, Anton J., Henri Spronk |
|---|---|
| Přispěvatelé: | Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP) |
| Předmět: |
heart atrium fibrillation
stimulation fibroblast dabigatran tissues rat proline proteinase activated receptor collagen synthesis mouse anticoagulant therapy phosphorylation cancer growth factor fibrosis goat heart rhythm thrombin inhibitor blood clotting factor thrombin hypercoagulability society inflammation heart atrium remodeling nadroparin wild type cerebrovascular accident |
| Zdroj: | University of Groningen Heart Rhythm, 11(5), 6-7. ELSEVIER SCIENCE INC |
| ISSN: | 1547-5271 |
| Popis: | Introduction: Atrial fibrillation (AF) induces a hypercoagulable state. Coagulation factors provoke pro-fibrotic, pro-hypertrophic, and pro-inflammatory responses in a variety of tissues by stimulation of protease-activated receptors. We studied whether hypercoagulability causes atrial fibrosis and promotes AF. Methods and Results: In mice with enhanced thrombin activity (TMpro/pro), inducibility of AF episodes induced by burst pacing was higher and duration of AF episodes was longer compared to wild type (episodes > 2s in 6 out of 10 versus 0 out of 10 in wild type). In isolated rat cardiac fibroblasts, thrombin (0.05units/ ml) enhanced the phosphorylation of the pro-fibrotic signaling molecules Akt and Erk, and increased expression of tumor growth factor β1 (2.7fold) and the pro-inflammatory factor MCP-1 (6.1fold). Thrombin also increased the incorporation of 3H-proline suggesting enhanced collagen synthesis by cardiac fibroblasts (2.5fold). All effects could be prevented by the direct thrombin inhibitor dabigatran. In 6 goats with persistent AF treated with fraxiparine, endomysial fibrosis and the complexity of the AF substrate were less pronounced compared to control animals (maximal conduction time 23.3±3.1ms in control versus 15.7±2.1ms in fraxiparine, p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|