SERUM-LIPID PROFILE DETERMINES PLATELET REACTIVITY TO NATIVE AND MODIFIED LDL-CHOLESTEROL IN HUMANS

The effects of thrombin (0.2 U/ml) and native (n-LDL), malondialdehyde -modified (MDA-LDL) and auto-oxidized (ox-LDL) low-density lipoprotein s (20 mu g of protein/ml) on platelet activation were evaluated in sev en hyperlipidemic patients and compared to seven controls (Easting ser um cholesterol 8.49 +/- 0.5 and 4.61 +/- 0.4 mM, respectively). Basal and thrombin-induced increases in platelet intracellular free calcium ion concentration ([Ca2+](i); fura-2) were similar in hyperlipidemic p atients and controls (45 +/- 5 vs 42 +/- 3 and 635 +/- 51 vs 599 +/- 6 9 mM, respectively). n-LDL, MDA-LDL and ox-LDL increased basal [Ca2+]( i) (16, 36 and 81 percent, p < 0.01 between LDL-types), increases were consistently smaller in patients. There was an inverse relationship b etween LDL-induced responses and fasting serum LDL cholesterol as well as LDL/HDL ratio.In conclusion, modified LDL activated platelets to a greater extent than n-LDL, suggesting different types of LDL-receptor s. Their agonistic effect was inversely related to the fasting serum l ipid profile, suggesting that blunting of platelet responses to LDL co uld represent a protective mechanism in hyperlipidemic patients.