title: Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin.
abstract: OBJECTIVE
  This study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties.
  
  
  METHODS
  APOE null mice at 6 and 15weeks of age were treated with melatonin at a dose of 0.1mg/kg/day or 10mg/kg/day. We evaluated both histopathological alterations in endothelial and vascular smooth muscle cells by CyPA and rolling mononuclear cell expression during the early phase of atherosclerosis development.
  
  
  RESULTS
  Our study showed that CyPA expression increases and may modulate inflammatory cell adhesion and interleukin-6 expression inducing vascular smooth muscle cell migration and inflammatory cell extravasation in a time-dependent manner. Moreover, we observed an indirect atheroprotective effect of melatonin on vascular injury; it inhibited CyPA mediated inflammatory cell extravasation and oxidative stress.
  
  
  CONCLUSIONS
  The melatonin treatment may represent a new atheroprotective approach that contributes to reducing the early phase of atherosclerosis involving the rolling of monocytes, their passage to subendothelial space and inhibition of CyPA expression.
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. rezzani@med.unibs.it
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stacchiotti
authors.forename: Luigi Fabrizio
authors.initials: LF
authors.lastname: Rodella
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D021984:Cyclophilin A / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D013997:Time Factors
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D015850:Interleukin-6; D021984:Cyclophilin A; D008550:Melatonin