title: Simvastatin reduces circulating plasminogen activator inhibitor 1 activity in volunteers with the metabolic syndrome.
abstract: BACKGROUND
  The Metabolic Syndrome (MS) confers an increased risk for diabetes and cardiovascular disease. We previously showed that simvastatin has concomitant benefits in reducing low-density lipoprotein (LDL)-cholesterol and inflammation in MS subjects. The levels of plasminogen activator inhibitor 1(PAI-1), soluble P-selectin (sP-selectin), and soluble CD40 ligand (sCD40L) play an important role in the development and progression of atherosclerosis. Their levels are increased in the MS. The current study was to investigate the effects of simvastatin on PAI-1, sP-selectin, and sCD40 ligand.
  
  
  METHODS
  Fifty subjects with MS were randomized into either placebo or simvastatin (40 mg/day) group for 8 weeks. Blood samples were obtained at baseline and at the end of the study. PAI-1 activity and sP-selectin and sCD40L levels were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  There was no baseline difference in any of the parameters studied. Compared to baseline, simvastatin significantly reduced (P < 0.05) the circulating PAI-1 activity (24.3 +/- 5.2 IU/mL at baseline vs. 21.4 +/- 3.9 IU/mL after 8 weeks of treatment). Simvastatin did not alter (P < 0.05) the levels of sP-selectin (111.4 +/- 35.9 ng/mL at baseline vs. 118.5 +/- 71.2 ng/mL after 8 weeks) or sCD40L (2.0 +/- 1.6 ng/mL at baseline vs. 1.5 +/- 1.0 ng/mL after 8 weeks).
  
  
  CONCLUSIONS
  Our data indicate that simvastatin therapy has significant effects on the fibrinolytic system in MS subjects as evidenced in a reduction in PAI-1 activity.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California, Davis, Medical Center, Sacramento, CA, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Jason
authors.initials: J
authors.lastname: Rockwood
authors.forename: Danielle
authors.initials: D
authors.lastname: Zak
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000175:diagnosis / Q000473:pathology; D023201:CD40 Ligand / Q000096:biosynthesis; D002318:Cardiovascular Diseases; D002448:Cell Adhesion; D005342:Fibrinolysis; D006801:Humans; D007249:Inflammation; D008024:Ligands; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism*; D008954:Models, Biological; D019007:P-Selectin / Q000096:biosynthesis; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012306:Risk; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D008024:Ligands; D019007:P-Selectin; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1; D023201:CD40 Ligand; D019821:Simvastatin