Atorvastatin reduces platelet-oxidized-LDL receptor expression in hypercholesterolaemic patients

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.

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.

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).

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.