INCREASED LEVELS OF SOLUBLE P-SELECTIN IN HYPERCHOLESTEROLEMIC PATIENTS

Background-Hypercholesterolemia is considered a major risk factor for the development of atherosclerosis. Enhanced lipid peroxidation and pe rsistent platelet activation can be observed in vivo in hypercholester olemic patients and may have pathophysiological implications in the oc currence of cardiovascular events. P-selectin may play an important ro le in the pathogenesis of multicellular events, including atherosclero sis. We studied the impact of hypercholesterolemia and oxidative stres s on plasma levels of P-selectin. Methods and Results-Plasma levels of P-selectin were measured by means of an enzyme immunoassay in 20 hype rcholesterolemic patients with no clinical evidence of cardiovascular disease and in 20 sex-and age-matched normocholesterolemic subjects. H ypercholesterolemic patients had higher levels of F-selectin compared with that of control subjects (98+/-61 versus 56+/-14 ng/mL; P=.001). They also displayed increased von Willebrand Factor (VWF) levels (176/-22 versus 119+/-12%; P=.0001). A direct correlation was observed bet ween P-selectin and LDL cholesterol levels (rho=.453). Administration of vitamin E (600 mg/d for 2 weeks) to hypercholesterolemic patients s ignificantly reduced plasma P-selectin (40%), and an inverse correlati on was observed between vitamin E and P-selectin plasma levels (rho=-. 446). Conclusions-Hypercholesterolemia is associated with elevated pla smatic P-selectin. Altered oxidative processes leading to endothelial dysfunction and persistent platelet activation may contribute to incre ased soluble P-selectin levels. P-selectin may be proposed as a marker of endothelial dysfunction in hypercholesterolemic patients.