Thrombin receptor PAR-1 activation on endothelial progenitor cells enhances chemotaxis-associated genes expression and leukocyte recruitment by a COX-2-dependent mechanism

摘要: Endothelial colony forming cells (ECFC) represent a subpopulation of endothelial progenitor involved in repair. The activation procoagulant mechanisms associated with the vascular wall’s inflammatory responses to injury plays crucial role induction and progression atherosclerosis. However, little is known about ECFC proinflammatory potential. To explore thrombin receptor PAR-1 effects on chemotaxis/recruitment capacity. expression 30 genes be inflammation chemotaxis was quantified by real-time qPCR. SFLLRN peptide (PAR-1-ap) resulted significant increase nine chemotaxis-associated expression, including CCL2 CCL3 whose receptors are present ECFC. Furthermore, COX-2 found dramatically up-regulated consequently activation. silencing specific COX-2-siRNA also triggered down-regulation target genes. Conditioned media (c.m.) from control-siRNA- COX-2-siRNA-transfected ECFC, stimulated or not PAR-1-ap, were produced tested capacity recruit leukocytes vitro as well muscle ischemic hindlimb preclinical model. c.m. PAR-1-ap abrogated when gene silenced (in terms U937 migration adhesion cells) vivo. Finally, postnatal vasculogenic stem cell derived infantile hemangioma tumor (HemSC) incubated increased leukocyte recruitment Matrigel® implant. increases chemotactic at sites through COX-2-dependent mechanism.