title: Inhibition of angiogenesis by platelets in systemic sclerosis patients.
abstract: BACKGROUND
  Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angiogenesis of human dermal microvascular endothelial cells (DMVECs) in a tubule formation assay and to characterize the secretion of profibrotic and proinflammatory cytokines in these platelets.
  
  
  METHODS
  We analyzed platelets obtained from 30 patients with SSc and 12 healthy control subjects. Angiogenesis was evaluated in vitro with a DMVEC tubule formation assay on Matrigel and platelet-derived angiogenic factors such as vascular endothelial growth factor (VEGF), 165b isoform (VEGF165b), and cytokine secretion was evaluated. Platelet serotonin content was also determined.
  
  
  RESULTS
  When DMVECs were incubated with SSc platelet releasates, tubule formation was significantly inhibited (p < 0.01, t test), and higher expression of endothelin-1 in these cells was observed compared with control subjects (p < 0.05, Mann-Whitney U test). In SSc platelet releasates, VEGF165b was significantly higher (p < 0.05, t test), and the VEGF165b/VEGF ratio was increased compared with that of control subjects. Higher secretion of transforming growth factor β (p < 0.01, t test) and CD40L (p < 0.01, t test) was observed compared with control subjects. Also, intraplatelet serotonin levels were lower in platelets obtained from patients with diffuse SSc compared with patients with limited SSc and control subjects (p < 0.05, t test).
  
  
  CONCLUSIONS
  Our findings suggest that antiangiogenic factors such as VEGF165b, together with proinflammatory and profibrotic factors secreted by platelets, can contribute to the progression of peripheral microvascular damage, defective vascular repair, and fibrosis in patients with SSc.
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago, Chile. dmhirigo@uc.cl.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hirigoyen
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago, Chile. pburgos@med.puc.cl.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Burgos
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago, Chile. mmezzano@uc.cl.
authors.forename: Veronica
authors.initials: V
authors.lastname: Mezzano
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago, Chile. jdurans@med.puc.cl.
authors.forename: Josefina
authors.initials: J
authors.lastname: Duran
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago, Chile. mbarrientosbarria@gmail.com.
authors.forename: Magaly
authors.initials: M
authors.lastname: Barrientos
authors.affiliation: Departamento de Hematología-Oncología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. saezcla@gmail.com.
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Saez
authors.affiliation: Departamento de Hematología-Oncología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. opanes@med.puc.cl.
authors.forename: Olga
authors.initials: O
authors.lastname: Panes
authors.affiliation: Departamento de Hematología-Oncología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. dmezzano@med.puc.cl.
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Marcoleta 350, Santiago, Chile. mitureta@med.puc.cl.
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Iruretagoyena
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D018836:Inflammation Mediators