Metalloproteinase 10(mmp-10): a new link between inflammation and thrombosis
- Autores: Sara Martínez de Lizarrondo Iriarte
- Directores de la Tesis: José Antonio Páramo Fernández (dir. tes.), Josune Orbe (codir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2011
- Idioma: español
- Tribunal Calificador de la Tesis: Matias Antonio Ávila Zaragozá (presid.), Nerea Varo Cenarruzabeitia (secret.), Joan Carles Reverter (voc.), Eduardo Angles Cano (voc.), Jose Martinez Gonzalez (voc.)
- Materias:
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- Resumen
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.
