BACKGROUND INFORMATION: Recent studies suggest that endothelial progenitor cells (EPCs) and platelets have an important role in repair following vascular injury. Although evidence suggest that platelets are essential in EPC attracting, homing and differentiation to the injury site; however, the platelet effects on EPC function in atherosclerosis have received less attention. In this context, we followed the consequences of circulating EPCs and platelet microparticles (PMPs) administration on platelet-EPC interaction in atherosclerosis and the involved mechanisms. The experiments were performed on Golden Syrian hamsters divided in five equal groups: control (C), hypertensive-hypercholesterolemic (HH), HH treated with EPCs (HH-EPCs) or PMPs (HH-PMPs) and HH treated with EPCs and PMPs (HH-EPCs-PMPs). RESULTS: Compared with C group, EPCs isolated from HH and HH-PMPs groups presented a reduction of endothelial nitric oxide synthase and vascular endothelial growth factor expressions and an increase in thrombospondin-1 expression and inflammatory molecule secretion: interleukin 8 (IL)-8, myeloperoxidase (MPO) and plasminogen activator inhibitor-1 (PAI-1). EPC administration had beneficial effects, the obtained results being similar with those from the C group, while the combination with PMPs did not improve the EPC influences. Static coincubation of EPCs from HH and HH-PMPs with analogous platelets resulted in an increased EPC adhesion/migration, and IL-8, monocyte chemotactic protein-1, regulated on activation, normal T expressed and secreted, MPO and PAI-1 release, explained by the platelet hyperaggregability induced by pronounced distribution of vasodilator-stimulated phosphoprotein and filamentous actin, and the secretion of proinflammatory factors: IL-1β, -6, -8, CD40 ligand. EPC therapy alone revealed an impaired platelet-EPC interaction directly correlated with the reduction of inflammatory markers and platelet aggregability. Moreover, in a dynamic flow system, EPCs and platelets from HH and HH-PMPs exhibited weakened interplay abilities, while EPC transplantation reinforces them. CONCLUSIONS: The present study demonstrates that HH animals revealed functional impairment of EPCs and platelets, which correlate with their reduced contribution to re-endothelialisation at the injury site, although in vitro exposure to immobilised platelets promotes their adhesion and migration. EPC administration alone recovers EPC/platelet functions and consolidates their interaction under dynamic flow conditions. These findings disclose new advances in understanding the platelet-EPC interaction and its role in the vascular repair.
BACKGROUND INFORMATION: Recent studies suggest that endothelial progenitor cells (EPCs) and platelets have an important role in repair following vascular injury. Although evidence suggest that platelets are essential in EPC attracting, homing and differentiation to the injury site; however, the platelet effects on EPC function in atherosclerosis have received less attention. In this context, we followed the consequences of circulating EPCs and platelet microparticles (PMPs) administration on platelet-EPC interaction in atherosclerosis and the involved mechanisms. The experiments were performed on Golden Syrian hamsters divided in five equal groups: control (C), hypertensive-hypercholesterolemic (HH), HH treated with EPCs (HH-EPCs) or PMPs (HH-PMPs) and HH treated with EPCs and PMPs (HH-EPCs-PMPs). RESULTS: Compared with C group, EPCs isolated from HH and HH-PMPs groups presented a reduction of endothelial nitric oxide synthase and vascular endothelial growth factor expressions and an increase in thrombospondin-1 expression and inflammatory molecule secretion: interleukin 8 (IL)-8, myeloperoxidase (MPO) and plasminogen activator inhibitor-1 (PAI-1). EPC administration had beneficial effects, the obtained results being similar with those from the C group, while the combination with PMPs did not improve the EPC influences. Static coincubation of EPCs from HH and HH-PMPs with analogous platelets resulted in an increased EPC adhesion/migration, and IL-8, monocyte chemotactic protein-1, regulated on activation, normal T expressed and secreted, MPO and PAI-1 release, explained by the platelet hyperaggregability induced by pronounced distribution of vasodilator-stimulated phosphoprotein and filamentous actin, and the secretion of proinflammatory factors: IL-1β, -6, -8, CD40 ligand. EPC therapy alone revealed an impaired platelet-EPC interaction directly correlated with the reduction of inflammatory markers and platelet aggregability. Moreover, in a dynamic flow system, EPCs and platelets from HH and HH-PMPs exhibited weakened interplay abilities, while EPC transplantation reinforces them. CONCLUSIONS: The present study demonstrates that HH animals revealed functional impairment of EPCs and platelets, which correlate with their reduced contribution to re-endothelialisation at the injury site, although in vitro exposure to immobilised platelets promotes their adhesion and migration. EPC administration alone recovers EPC/platelet functions and consolidates their interaction under dynamic flow conditions. These findings disclose new advances in understanding the platelet-EPC interaction and its role in the vascular repair.