Tesis doctoral de Jorge Cerveró García
Atrial fibrillation (af) is the most commonly sustained cardiac arrhythmia in clinical practice. The relevance of af is emphasized by the fact that this pathology is one of the most important risk factors for cardioembolic stroke, which is one of the leading causes of death in the developed world. the endocardial behaviour during af has been hardly explored, in spite of endothelial injury being one of the three contributors to thrombogenesis in the virchow¿s triad. Moreover, thrombi in af patients are usually found in the left atrium rather than the right one, even although both cavities experience the same arrhythmic process. In spite of this notion is widely accepted, little research has been performed in order to look for mechanisms to explain it. under the hypothesis that there are mechanisms triggered by af in the left atrial endothelium which contribute to the thrombogenic process, this work has approached the following objectives: 1) to study the anticoagulant protein c pathway in the healthy atrial tissue in non human primates (macaca fascicularis), looking for differences between left and right endocardium. 2) to approach the alterations induced during af in the endocardium by using gene expression microarray technology in a porcine model of rapid atrial pacing (rap), which resembles af. On one hand by comparing the endocardial expression pattern between rap-exposed and control pigs and on the other one by comparing the endocardial expression changes in the left and right atria upon rap exposure. first, interestingly, the ex vivo assays using the endocardial cells of the macaques revealed that the left atrial endothelial cells exhibit less ability than the right ones to activate protein c (i.E. Their anticoagulant capacity is poorer), most probably due to their lower thrombomodulin expression, as assessed by immunofluorescence. second, the increase in d-dimer and in e-nos expression in the rap-exposed pigs suggested that this approach is suitable for studying the af-evoked endocardial changes. Rap-stimulation induced the up and down-regulation of different genes, a portion of which are involved in mechanisms related to hemostasis and inflammation. Changes were more dramatic in the left than in the right atrial cells. therefore, this work provides new potential targets to better know the prothrombotic processes linked to af, that deserve a subsequent and deeper approach.
Datos académicos de la tesis doctoral «Contribución del endocardio a la trombogenicidad asociada a la fibrilación auricular«
- Título de la tesis: Contribución del endocardio a la trombogenicidad asociada a la fibrilación auricular
- Autor: Jorge Cerveró García
- Universidad: Navarra
- Fecha de lectura de la tesis: 25/05/2012
Dirección y tribunal
- Director de la tesis
- José María Hermida Santos
- Tribunal
- Presidente del tribunal: José Antonio Paramo fernandez
- María del pilar Medina badenes (vocal)
- José ramón González porras (vocal)
- Francisco Velasco gimena (vocal)