title: Niacin reverses migratory macrophage foam cell arrest mediated by oxLDL in vitro.
abstract: BACKGROUND
  Niacin reduces vascular oxidative stress and down regulates inducible nitric oxide synthase, an enzyme mediating proatherosclerotic effects in part by increasing oxidative stress. Here, we evaluate whether Niacin reverses the redox sensitive migratory arrest of macrophages in response to oxidised(ox) LDL uptake.
  
  
  METHODS
  Migration of RAW264.7 cells, a murine macrophage cell line and bone marrow derived macrophages from wildtype and iNOS knockout mice was quantified using a modified Boyden chamber. Unstimulated cells or cells preincubated with oxLDL or non-oxidised (n)LDL were treated with Nicotinic acid or Nicotinamide. Nitric oxide, peroxynitrite and ROS production were assessed using electron paramagnetic resonance (ESR). Additionally, flow cytometry analysis of apoptosis, fokal adhesion kinase (FAK), phalloidin, CD36, F4/80 macrophage marker and iNOS gene expression (PCR) were assessed.
  
  
  RESULTS
  Migration of Nicotinic acid, Nicotinamide treated cells or unstimulated cells did not differ (P>0.05). oxLDL treatment significantly reduced migration vs. unstimulated cells (p<0.05). In contrast, migratory arrest in response to oxLDL treatment was reversed by co-incubation with Nicotinic acid and Nicotinamide. The oxLDL-induced peroxynitrite formation in RAW264.7 cells was abolished by Niacin and glutathion (GSH) oxidation was significantly reduced. However, nitric oxide (NO)- and reactive oxygen species (ROS) production induced by oxLDL were not affected by Niacin treatment of RAW264.7 cells. In addition, Nicotinic acid and Nicotinamide reduced actin polymerization, a marker for migratory arrest.
  
  
  CONCLUSIONS
  Our data shows that oxLDL induced inhibition of macrophage migration in vitro can be reversed by Niacin. Furthermore, Niacin reduces peroxynitite formation and improves antioxidant GSH.
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Koelle
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Fendler
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Schroettle
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Czihal
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, University Hospital Munich, Munich, Germany.
authors.forename: Peter Jan
authors.initials: PJ
authors.lastname: Kuhlencordt
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009525:Niacin / Q000494:pharmacology*; D010084:Oxidation-Reduction
chemical_list: D008077:Lipoproteins, LDL; D009525:Niacin