Tesis doctoral de Sara Martínez De Lizarrondo Iriarte
We have explored the role of metalloproteinase-10 (mmp-10) or stromelysin-2 in studies in vitro and in vivo and its possible association with thrombotic events. in vitro studies demonstrated that proinflammatory and prothrombotic stimuli, as thrombin and cd40l up-regulate endothelial mmp-10 expression. We described for the first time the synergistic effect of both stimuli on mmp-10 production via par-1-mediated mechanism, and identified the activation of mapk pathways implicated. in vivo studies indicated that thrombin and cd40l co-administration induce vascular expression of mmp-10 in wild-type mice. we have measured circulating mmp-10 levels in patients with clinical conditions characterized by enhanced thrombin generation. In these clinical settings, a significant increase in mmp-10 levels was found. These findings point out mmp-10 as a novel biomarker for cardiovascular disorders. finally, we observed a significative increment on endothelial microparticle generation after thrombin/cd40l stimulation. We also demonstrated that these particles harbored mmp-10 activity, which could be regarded as facilitators of endogenous fibrinolysis in conditions characterized by excessive thrombin generation. in summary, these findings reveal a novel interaction between thrombin and cd40l signaling pathways, and establish a new link between inflammation and thrombosis involving mmp-10, which may have relevant pathophysiological and therapeutic implications.
Datos académicos de la tesis doctoral «Metalloproteinase 10(mmp-10): a new link between inflammation and thrombosis«
- Título de la tesis: Metalloproteinase 10(mmp-10): a new link between inflammation and thrombosis
- Autor: Sara Martínez De Lizarrondo Iriarte
- Universidad: Navarra
- Fecha de lectura de la tesis: 21/02/2011
Dirección y tribunal
- Director de la tesis
- José Antonio Paramo Fernandez
- Tribunal
- Presidente del tribunal: matías Antonio ávila zaragozá
- José María Martínez gonzález (vocal)
- joan carles Reverter (vocal)
- eduardo Angles-cano (vocal)