title: Dose-dependent effect of rosuvastatin in the regulation of metalloproteinase expression.
abstract: BACKGROUND
  The importance of rosuvastatin at therapeutic dosage in regulating the release, activity, protein level, and expression of matrix metalloproteinases (MMP)-2 and MMP-9 was investigated.
  
  
  METHODS
  Human umbilical artery smooth muscle cells were stimulated, in vitro, in a serum-free medium with rosuvastatin at various concentrations (2, 4, 7, and 10 ng/mL, which correspond to the maximal plasma concentration observed in healthy men after a daily oral intake of 5, 10, 20, and 40 mg, respectively). The release of MMP-2 and MMP-9 in the conditioned medium was assessed by enzyme-linked immunosorbent assay and confirmed by Western blot, the activity and expression were determined by zymography and polymerase chain reaction, respectively.
  
  
  RESULTS
  Human umbilical artery smooth muscle cells stimulated with rosuvastatin at 7 and 10 ng/mL had a significant lower release, activity, protein level, and expression of MMP-2 and MMP-9, when compared with those stimulated at 2 and 4 ng/mL (MMP-2 =p < 0.0001 and p < 0.0001, respectively; MMP-9 =p < 0.0001 and p < 0.0001, respectively).
  
  
  CONCLUSIONS
  The effects of rosuvastatin in reducing MMP-2 and MMP-9, which might stabilize the atherosclerotic plaques, are dose-dependent.
authors.affiliation: Department of Surgery Pietro Valdoni, University of Rome Sapienza, Rome, Italy. paolo.sapienza@uniroma1.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Sapienza
authors.forename: Valeria
authors.initials: V
authors.lastname: Borrelli
authors.forename: Antonio V
authors.initials: AV
authors.lastname: Sterpetti
authors.forename: Simona
authors.initials: S
authors.lastname: Dinicola
authors.forename: Elvira
authors.initials: E
authors.lastname: Tartaglia
authors.forename: Luca
authors.initials: L
authors.lastname: di Marzo
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects / Q000201:enzymology
chemical_list: D017077:Culture Media, Conditioned; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9