title: Nifedipine improves the migratory ability of circulating endothelial progenitor cells depending on manganese superoxide dismutase upregulation.
abstract: BACKGROUND
  Migratory ability of resident endothelial cells and their circulating progenitors, that is endothelial progenitor cells (EPCs), represent a crucial event in vascular repairing processes. Although oxidants are known to counteract the migratory ability of resident endothelial cells, their possible role in modulating EPC motility is unknown. EPCs exhibit stronger resistance to oxidants than mature endothelial cells mainly because of higher expression of manganese (Mn) superoxide dismutase (SOD). As nifedipine is a dihydropyridine calcium antagonist known to enhance MnSOD expression in mature endothelial cells, we investigated the effects of nifedipine on MnSOD expression and motility in EPCs.
  
  
  RESULTS
  EPCs were isolated from peripheral blood of healthy donors and cultured in fibronectin-coated flasks. Nifedipine improved both motility of cultured EPCs (+55% vs. control, P = 0.007) and their adhesion to tumor necrosis factor-alpha-activated mature endothelial cells (+33% vs. control, P = 0.03). Reduction of EPC dichlorofluorescein content (-32% vs. control, P = 0.009) and a parallel increase in nitrite plus nitrate concentration in EPC supernatants (+25% vs. control, P = 0.009) were also observed. The study of SOD showed a nifedipine-dependent upregulation of MnSOD in a time-dependent and dose-dependent manner. MnSOD expression blockade by RNA interference abolished nifedipine effect on EPC motility. Although nifedipine also increased vascular endothelial growth factor (VEGF) release from EPCs, its effect on EPC motility was unaffected by an anti-VEGF antibody.
  
  
  CONCLUSIONS
  Nifedipine improves EPC motility due to MnSOD upregulation. The capability of this dihydropyridine calcium antagonist to reduce cardiovascular events might also be related to improved EPC function.
authors.affiliation: Department of Internal Medicine and Public Health, University of L'Aquila, L'Aquila, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Passacquale
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Desideri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Croce
authors.forename: Simona
authors.initials: S
authors.lastname: Murgo
authors.forename: Maria Michela
authors.initials: MM
authors.lastname: Mancarelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Zazzeroni
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferri
mesh_terms: D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D009566:Nitrates; D009573:Nitrites; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013482:Superoxide Dismutase; D009543:Nifedipine