title: Atorvastatin reduces platelet-oxidized-LDL receptor expression in hypercholesterolaemic patients.
abstract: BACKGROUND
  Oxidized-LDL (ox-LDL) are proatherogenic and platelet-activating molecules. Atorvastatin reduces platelet activity before cholesterol-lowering action. CD36 and lectin-like oxidized-LDL receptor-1 (LOX-1) are specific ox-LDL receptors expressed also in platelets. This study was planned to address whether the possible rapid effect of atorvastatin on platelets could be related to modulation of ox-LDL receptors.
  
  
  METHODS
  Forty-eight hypercholesterolaemic subjects requiring statin treatment (atorvastatin 20 mg day(-1)) after an ineffective diet regimen were evaluated for complete lipid-profile (chromogenic); P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection); circulating and platelet-associated ox-LDL (ox- and Pox-LDL, ELISA); and intracellular citrullin recovery (iCit, HPLC) at baseline and 3, 6 and 9 days after inclusion in the study. Moreover, we studied 48 normal controls matched for sex and age.
  
  
  RESULTS
  Platelet activity expressed by P-sel (in resting and thrombin-activated cells), CD36 and LOX-1 were increased in hypercholesterolaemic subjects (all P < 0.01). Atorvastatin induced a reduction of CD36 at 6 days (P < 0.05); and P-sel in resting (P < 0.001) and activated cells (P < 0.001) and LOX-1 were reduced at 9 days (all P < 0.001) in association with decreased Pox-LDL (P < 0.001) and increased iCit (P < 0.01). All data were obtained before a significant reduction of LDL and ox-LDL was achieved (P = 0.109 and 0.113).
  
  
  CONCLUSIONS
  Present data suggest that platelet deactivation by atorvastatin is related to CD36 and LOX-1 expression reduction before significant LDL changes. Moreover, the modulation of LOX-1 can be considered a self-relevant antiatherothrombotic action of atoravastin owing to the important role of this receptor in the ox-LDL-mediated vascular damage.
authors.affiliation: University of Siena, Siena, Italy. puccetti@unisi.it
authors.forename: L
authors.initials: L
authors.lastname: Puccetti
authors.forename: T
authors.initials: T
authors.lastname: Sawamura
authors.forename: A L
authors.initials: AL
authors.lastname: Pasqui
authors.forename: M
authors.initials: M
authors.lastname: Pastorelli
authors.forename: A
authors.initials: A
authors.lastname: Auteri
authors.forename: F
authors.initials: F
authors.lastname: Bruni
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D018955:CD36 Antigens / Q000097:blood; D002956:Citrulline / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D011758:Pyrroles / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000097:blood / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E
chemical_list: D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D019007:P-Selectin; D011758:Pyrroles; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D002956:Citrulline; D000069059:Atorvastatin; D019001:Nitric Oxide Synthase