Lysine Modification of LDL or Lipoprotein(a) by 4-Hydroxynonenal or Malondialdehyde Decreases Platelet Serotonin Secretion Without Affecting Platelet Aggregability and Eicosanoid Formation

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Abstract
Abstract The effects of lysine-modified atherogenic plasma lipoproteins, known to be constituents of human atherosclerotic plaques, were studied on platelet function in vitro. LDL and lipoprotein(a) [Lp(a)] modified with secondary breakdown products of lipid peroxidation (4-hydroxy-2,3- trans -nonenal [HNE] 0.1 to 10 mmol/L or malondialdehyde [MDA] 1 to 50 mmol/L) induced neither spontaneous platelet aggregation nor secretion of 5-hydroxytryptamine (5-HT) from platelet amine-storage granules. Incubation of platelets with HNE- or MDA-modified LDL or Lp(a) (up to 1200 μg protein/mL) prior to thrombin (0.2 U/mL)– or collagen (2 μg/mL)–induced aggregation did not enhance platelet aggregability or formation of eicosanoids, ie, thromboxane A 2 or prostaglandins E 2 and F 2α . In contrast to native lipoproteins, HNE- or MDA-modified LDL and Lp(a) (≈20% to 30% of total apolipoprotein lysine residues modified) exerted a pronounced dose-dependent inhibition of 5-HT release from activated platelets in the following order: HNE LDL (50%)>HNE Lp(a) (40%)>MDA LDL (20%)>MDA Lp(a) (5%). Preincubation of human blood platelets with acetylated LDL or Lp(a) (≈60% to 70% of total lysine residues modified) prior to aggregation impaired serotonin secretion by 50% compared with native LDL or Lp(a). These findings suggest that the interaction of platelets with aldehyde-modified atherogenic plasma lipoproteins should not necessarily be considered as proatherogenic with respect to the effects observed in our in vitro studies.