title: Interaction of platelets with endothelial progenitor cells in the experimental atherosclerosis: Role of transplanted endothelial progenitor cells and platelet microparticles.
abstract: BACKGROUND
  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.
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Alexandru
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
authors.forename: Eugen
authors.initials: E
authors.lastname: Andrei
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Dragan
authors.affiliation: Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
authors.forename: Adriana
authors.initials: A
authors.lastname: Georgescu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016209:Interleukin-8; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017395:Plasminogen Activator Inhibitor 1; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D000098662:Vasodilator-Stimulated Phosphoprotein; D023201:CD40 Ligand; D009195:Peroxidase; D052250:Nitric Oxide Synthase Type III
keywords: Animal models; Cardiovascular risk factors; Endothelial progenitor cells; Platelets