Core aldehydes of alkyl glycerophosphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial relaxation

Plaque disruption with superimposed thrombo- sis is considered to be responsible for precipitating acute coronary syndrome. We identified sn -1-alkyl- and sn -1-acyl- type glycerophosphocholine (GroPCho) core aldehydes from human atheromas and demonstrated their activities on platelets and arteries. The naturally occurring core alde- hydes were identified and quantified in relation to synthetic standards by high performance liquid chromatography with on-line electrospray mass spectrometry. 1- O -Hexadecyl-2-(5- oxovaleroyl)- sn -GroPCho (C 5 alkyl GroPCho core aldehyde), occurring in atheroma at less than 0.1% of total phosphatide, induced aggregation of washed rabbit platelets (50% effec- tive dose was approximately 50 nM). Aggregations induced by C 5 alkyl GroPCho core aldehydes were completely inhibited by two different platelet-activating factor receptor antagonists. 1-Palmitoyl-2-(5-oxovaleroyl)- sn -GroPCho (C 5 acyl GroPCho core aldehyde) induced platelet shape change, but not aggre- gation. By contrast, 10 m M C 5 alkyl and C 5 acyl GroPCho core aldehydes both inhibited endothelium-dependent relaxation of rabbit artery by 50% (endothelium-independent relaxation was not affected). The present demonstration of platelet ag- gregation by physiologically relevant concentrations of alkyl GroPCho core aldehydes suggests that alkyl GroPCho core al- dehyde generated in atheroma could be involved in precipitat- ing acute coronary events, in which thrombus formation fol- lowing lipid-rich plaque disruption plays an important role. — Kamido, H., H. Eguchi, H. Ikeda, T. Imaizumi, K. Yamana, K. Hartvigsen, A. Ravandi, and A. Kuksis. Core aldehydes of alkyl glycerophosphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial re- laxation. J. Lipid Res. 2002. 43: 158-166.