Roles of mechanical force and CXCR1/CXCR2 in shear-stress-induced endothelial cell migration.

We previously demonstrated that CXCR1 and CXCR2 are novel mechanosensors mediating laminar shear-stress-induced endothelial cell (EC) migration (Zeng et al. in Cytokine 53:42-51, 2011). In the present study, an analytical model was proposed to further analyze the underlying mechanisms, assuming the mechanical force (MF) and mechanosensor-mediated biochemical reactions induce cell migration together. Shear stress can regulate both mechanosensor-mediated migration in the flow direction (Ms-M(FD)) and mechanosensor-mediated migration toward a wound (Ms-M(W)). Next, the migration distance, the roles of MF-induced cell migration (MF-M), and the mobilization mechanisms of mechanosensors were analyzed. The results demonstrated that MF-M plays an important role in 15.27 dyn/cm(2) shear-stress-induced EC migration but is far weaker than Ms-M(W) at 5.56 dyn/cm(2). Our findings also indicated that CXCR2 played a primary role, in synergy with CXCR1. The Ms-M(FD) was primarily mediated by the synergistic effect of CXCR1 and CXCR2. In Ms-M(W), when shear stress was beyond a certain threshold, the synergistic effect of CXCR1 and CXCR2 was enhanced, and the effect of CXCR1 was inhibited. Therefore, the retarding of EC migration and wound closure capacity under low shear flow was related to the low magnitude of shear stress, which may contribute to atherogenesis and many other vascular diseases.