Lysine modification of LDL or lipoprotein(a) by 4-hydroxynonenal or malondialdehyde decreases platelet serotonin secretion without affecting platelet aggregability and eicosanoid formation.
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 aminestorage granules. Incubation of platelets with HNE- or MDA-modified LDL or Lp(a) (up to 1200 micrograms protein/mL) prior to thrombin (0.2 U/mL)- or collagen (2 micrograms/mL)-induced aggregation did not enhance platelet aggregability or formation of eicosanoids, ie, thromboxane A2 or prostaglandins E2 and F2 alpha. In contrast to native lipoproteins, HNE- or MDA-modified LDL and Lp(a) (approximately 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) (approximately 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.
Malle
E
E
Karl-Franzens University, Institute of Medical Biochemistry, Graz, Austria.
Ibovnik
A
A
Leis
H J
HJ
Kostner
G M
GM
Verhallen
P F
PF
Sattler
W
W
D000107:Acetylation; D000447:Aldehydes / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D015777:Eicosanoids / Q000096:biosynthesis; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism*; D008315:Malondialdehyde / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*
D000447:Aldehydes; D015777:Eicosanoids; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; C032629:acetyl-LDL; D012701:Serotonin; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal; D008239:Lysine