title: Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects.
abstract: Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.
authors.affiliation: Department of Clinical Medicine and Immunological Sciences, Internal Medicine Division, Center for Atherosclerosis Research, University of Siena, Siena, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Bruni
authors.forename: Anna Laura
authors.initials: AL
authors.lastname: Pasqui
authors.forename: Marcello
authors.initials: M
authors.lastname: Pastorelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bova
authors.forename: Michela
authors.initials: M
authors.lastname: Cercignani
authors.forename: Alberto
authors.initials: A
authors.lastname: Palazzuoli
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: W R
authors.initials: WR
authors.lastname: Gioffre
authors.forename: Alberto
authors.initials: A
authors.lastname: Auteri
authors.forename: Luca
authors.initials: L
authors.lastname: Puccetti
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D018955:CD36 Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C495137:OLR1 protein, human; D019007:P-Selectin; D051127:Scavenger Receptors, Class E; D013917:Thrombin