Identificación y caracterización funcional de nuevos genes implicados en el ictus cardioembólico

Résumé

Cardioembolic stroke accounts for about one fifth of ischaemic strokes and atrial fibrillation (AF) is its main cause. Molecular pathways for the development of cardioembolic stroke in AF patients are poorly understood. We aimed to define a gene expression profiles in blood cells that differentiate cardioembolic stroke from no cardioembolic stroke in AF patients. Gene expression profile (282 probes) in the blood of AF patients distinguished cardioembolic stroke patients from those without cardioembolic stroke history with a 100% specificity and sensibility. One of these genes, hspa1b, was studied in a larger population. Again, higher expression of hspa1b gene was associated with a reduced risk of cardioembolic stroke [adjusted odds ratio (95% confidence interval) = 0.21 (0.09-0.51)]. Hspa1b codifies for heat shock protein 70 (HSP70). The possible HSP70 antithrombotic function was studied in different animal models of thrombosis. HSP70 knock out (HSP70 KO) mice developed thrombosis earlier than wild type (WT) mice. HSP70 KO mice exhibited normal haemostatic parameters (PT,, APTT) as well as tail bleeding time. Finally, endothelial cells from HSP70 KO mice were proner to apoptosis than cell from WT animals (p=0.05). In summary, we found that hspa1b expression is associated with a decreased risk of cardioembolic stroke. HSP70 protected against thrombosis in murine models without increasing the haemorrhagic tendency. We propose that reduction of apoptosis in endothelial cells could be the mechanism of antithrombotic properties of HSP70.