title: Tissue factor regulates microvessel formation and stabilization by induction of chemokine (C-C motif) ligand 2 expression.
abstract: OBJECTIVE
  Tissue factor (TF) triggers arterial thrombosis. TF is also able to initiate cellular signaling mechanisms leading to angiogenesis. Because high cardiovascular risk atherosclerotic plaques show significant angiogenesis, our objective was to investigate whether TF is able to trigger and stabilize atherosclerotic plaque neovessel formation.
  
  
  RESULTS
  In this study, we showed, by real-time confocal microscopy in 3-dimensional basement membrane cocultures, that TF in human microvascular endothelial cells (HMEC-1) and in human vascular smooth muscle cells (HVSMCs) plays an important role in the formation of capillary-like networks. TF silencing in endothelial cells and smooth muscle cells inhibits the formation of tube-like structures with stable phenotype. Using an in vivo model, we observed that TF inhibition in either HMEC-1 or HVSMCs reduced their shared ability to form new capillaries. The phenotypic changes induced by TF silencing were linked to reduced chemokine (C-C motif) ligand 2 (CCL2) expression in endothelial cells. Wound healing and chemotactic assays demonstrated that TF-induced release of CCL2 stimulated HVSMC migration to HMEC-1.
  
  
  CONCLUSIONS
  Endogenous TF regulates CCL2 production in endothelial cells. Secreted CCL2 mediates the angiogenic effect of TF by recruiting smooth muscle cells toward endothelial cells and facilitates the maturation of newly formed microvessels.
authors.affiliation: Cardiovascular Research Center, Hospital de Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Arderiu
authors.forename: Esther
authors.initials: E
authors.lastname: Peña
authors.forename: Rosa
authors.initials: R
authors.lastname: Aledo
authors.forename: Oriol
authors.initials: O
authors.lastname: Juan-Babot
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D013925:Thromboplastin