title: N-3 PUFA increase bioavailability and function of endothelial progenitor cells.
abstract: OBJECTIVE
  Recent data suggest that n-3 PUFA exert beneficial effects on endothelial progenitor cell (EPC) biology. We sought to investigate whether these effects might be mediated by enhanced EPC in vitro function and/or in vivo bioavailability.
  
  
  RESULTS
  CACs and late-outgrowth EPCs were isolated from peripheral blood mononuclear cells obtained from 12 donor buffy-coats. The effect of n-3 PUFA (EPA:DHA = 0.9:1.5; 9 μM EPA plus 15 μM DHA) was tested on CAC/EPC viability, function (tube-formation) and pro-inflammatory molecule expression. Circulating EPC (cells positive for CD34, CD133 and kinase insert domain receptor - KDR cell-surface antigens by flow cytometry) number was evaluated in 20 healthy subjects (10 F/10 M, 32 ± 5 years), randomized to receive 4 mackerel or sardine portions per week for 6 weeks followed by a 6 week free-diet period. N-3 PUFA improved CAC and late-outgrowth EPC viability (p < 0.05) and the capacity to form tube-like structures in CACs (+38%; p < 0.05) and late-outgrowth EPCs (+15%; p < 0.05). ICAM-1 expression was reduced in both CACs (p < 0.05) and late-outgrowth EPCs (p < 0.05) and VCAM-1 in late-outgrowth EPCs (p < 0.005). N-3 PUFA significantly decreased TNF-α and MCP-1 expression in CACs and IL-8, TNF-α and MCP-1 in late-outgrowth EPCs (p < 0.05). Circulating EPC number significantly improved after 6 weeks of a fish-enriched diet (p < 0.01) and returned to baseline levels after a 6 week free-diet period (p < 0.01). Plasma EPA levels were independently and positively associated with EPC levels (p < 0.005).
  
  
  CONCLUSIONS
  Our findings support the case of a beneficiary role played by n-3 PUFA in EPC function and bioavailability.
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health. University of Brescia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Spigoni
authors.forename: Carlo
authors.initials: C
authors.lastname: Lombardi
authors.forename: Monia
authors.initials: M
authors.lastname: Cito
authors.forename: Angela
authors.initials: A
authors.lastname: Picconi
authors.forename: Valentina
authors.initials: V
authors.lastname: Ridolfi
authors.forename: Roberta
authors.initials: R
authors.lastname: Andreoli
authors.forename: Nadia
authors.initials: N
authors.lastname: Anelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Ivana
authors.initials: I
authors.lastname: Zavaroni
authors.forename: Riccardo
authors.initials: R
authors.lastname: Raddino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dei Cas
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000097:blood*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005399:Fishes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017747:Seafood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D040301:Vascular Endothelial Growth Factor Receptor-2