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Journal of Lipid Research, Vol. 43, 158-166, January 2002
Copyright © 2002 by Lipid Research, Inc.
Core aldehydes of alkyl glycerophosphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial relaxation
Hiroshi Kamidoa,
Hiroyuki Eguchib,
Hisao Ikedab,
Tsutomu Imaizumib,
Kazunari Yamanac,
Karsten Hartvigsend,
Amir Ravandid, and
Arnis Kuksisd
a Fourth Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
b Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
c Second Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
d Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada
Correspondence to:
Hiroshi Kamido, at Midori Health Care Foundation, 3-22-5 Tarumi-cho, Suita, Osaka 564-0062, Japan., hkamido-midori{at}umin.ac.jp (E-mail)
Plaque disruption with superimposed thrombosis 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 aldehydes 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 (C5 alkyl GroPCho core aldehyde), occurring in atheroma at less than 0.1% of total phosphatide, induced aggregation of washed rabbit platelets (50% effective dose was approximately 50 nM). Aggregations induced by C5 alkyl GroPCho core aldehydes were completely inhibited by two different platelet-activating factor receptor antagonists. 1-Palmitoyl-2-(5-oxovaleroyl)-sn-GroPCho (C5 acyl GroPCho core aldehyde) induced platelet shape change, but not aggregation. By contrast, 10 µM C5 alkyl and C5 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 aggregation by physiologically relevant concentrations of alkyl GroPCho core aldehydes suggests that alkyl GroPCho core aldehyde generated in atheroma could be involved in precipitating acute coronary events, in which thrombus formation following 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 relaxation. J. Lipid Res. 2002. 43: 158 166.
Supplementary key words:
acute coronary syndrome, glycerophosphocholine, lipid peroxidation, mass spectrometry, phospholipid, platelet-activating factor

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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