title: Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.
abstract: BACKGROUND
  Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation.
  
  
  METHODS
  Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment.
  
  
  RESULTS
  PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05).
  
  
  CONCLUSIONS
  The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.
authors.affiliation: Department of Clinical Medicine and Immunological Sciences, Internal Medicine Division, Center for Metabolic Diseases and Atherosclerosis, University of Siena, Policlinico Le Scotte, V.le Bracci, 53100 Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bruni
authors.forename: A L
authors.initials: AL
authors.lastname: Pasqui
authors.forename: M
authors.initials: M
authors.lastname: Pastorelli
authors.forename: G
authors.initials: G
authors.lastname: Bova
authors.forename: M
authors.initials: M
authors.lastname: Di Renzo
authors.forename: M
authors.initials: M
authors.lastname: Cercigani
authors.forename: A
authors.initials: A
authors.lastname: Leo
authors.forename: A
authors.initials: A
authors.lastname: Auteri
authors.forename: L
authors.initials: L
authors.lastname: Puccetti
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000069059:Atorvastatin; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D018709:Statistics, Nonparametric
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin