Serum Lipid Profile Determines Platelet Reactivity to Native and Modified LDL-Cholesterol in Humans

 

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Summary

The effects of thrombin (0.2 U/ml) and native (n-LDL), malon- dialdehyde-modified (MDA-LDL) and auto-oxidized (ox-LDL) low-density lipoproteins (20 μg of protein/ml) on platelet activation were evaluated in seven hyperlipidemic patients and compared to seven controls (fasting serum 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⁺; fura-2) were similar in hyperlipidemic patients and controls (45 ± 5 vs 42 ± 3 and 635 ±51 vs 599 ± 69 mM, respectively). n-LDL, MDA-LDL and ox-LDL increased basal [Ca²⁺]; (16, 36 and 81 percent, p <0.01 between LDL-types), increases were consistently smaller in patients. There was an inverse relationship between 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-receptors. Their agonistic effect was inversely related to the fasting serum lipid profile, suggesting that blunting of platelet responses to LDL could represent a protective mechanism in hyperlipidemic patients.

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