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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:377-384.)
© 1995 American Heart Association, Inc.

Articles

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

Ernst Malle; Anton Ibovnik; Hans J. Leis; Gerhard M. Kostner; Peter F. J. Verhallen; Wolfgang Sattler

From the Karl-Franzens University, Institute of Medical Biochemistry (E.M., A.I., G.M.K., W.S.), and the Institute of Paediatrics (H.J.L.), Department of Mass Spectrometry, Graz, Austria, and the Research Laboratories of Schering AG (P.F.J.V.), Berlin, FRG.

Correspondence to Ernst Malle, Karl-Franzens University, Institute of Medical Biochemistry, Harrachgasse 21, A-8010 Graz, Austria.

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 A₂ or prostaglandins E₂ and F₂. 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.

Key Words: platelet-lipoprotein interaction • acetylation • dense-granule secretion • eicosanoids • gas chromatography–mass spectrometry

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