title: Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis.
abstract: BACKGROUND
  Thrombospondin 1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration and intimal hyperplasia. Statins and nitric oxide (NO) donors decrease intimal hyperplasia. We previously showed that statins (long-term exposure) and NO donors inhibit TSP-1-induced VSMC chemotaxis.
  
  
  OBJECTIVE
  (1) Pretreatment with short-term statin will inhibit TSP-1-induced VSMC chemotaxis and (2) NO donors will enhance statin inhibition of TSP-1-induced or platelet-derived growth factor (PDGF)-induced VSMC chemotaxis.
  
  
  METHODS
  We examined these treatment effects on TSP-1-induced VSMC chemotaxis: (1) long-term (20 hours) versus short-term (20 minutes) pravastatin, (2) diethylenetriamine NONOate (DETA/NO) or S-nitroso-N-acetylpenicillamine (SNAP) in combination with pravastatin, and (3) comparison of TSP-1 to PDGF as a chemoattractant.
  
  
  RESULTS
  Pravastatin (long term or short term) inhibited TSP-1-induced chemotaxis. Diethylenetriamine NONOate and SNAP impeded statin inhibition of TSP-1-induced chemotaxis. Platelet-derived growth factor and TSP-1 had opposite effects on DETA/NO-pravastatin treatment.
  
  
  CONCLUSIONS
  Short-term statin pretreatment inhibited TSP-1-induced VSMC chemotaxis, suggesting a pleiotropic effect. High-dose NO reversed statin inhibition of TSP-1-induced chemotaxis, suggesting NO and statin combination therapies warrant further study.
authors.affiliation: Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Seymour
authors.affiliation: Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stein
authors.affiliation: Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Han
authors.affiliation: Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA.
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Maier
authors.affiliation: Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA gahtanv@upstate.edu.
authors.forename: Vivian
authors.initials: V
authors.lastname: Gahtan
mesh_terms: D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000378:metabolism / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010982:Platelet-Derived Growth Factor; D019700:Thrombospondin 1; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D017035:Pravastatin
keywords: migration; nitric oxide; statins; thrombospondin; vascular smooth muscle cells