Core aldehydes of alkyl glycerophosphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial relaxation.
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 (C(5) 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 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 aggregation. By contrast, 10 microM 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 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
Hiroshi
H
Fourth Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan. hkamido-midori@umin.ac.jp
Eguchi
Hiroyuki
H
Ikeda
Hisao
H
Imaizumi
Tsutomu
T
Yamana
Kazunari
K
Hartvigsen
Karsten
K
Ravandi
Amir
A
Kuksis
Arnis
A
D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D001158:Arteries / Q000502:physiology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000138:chemical synthesis; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D012015:Reference Standards; D014664:Vasodilation / Q000502:physiology*
C452581:1-O-hexadecyl-2-(5-oxovaleroyl)-sn-glycerophosphocholine; C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D000447:Aldehydes; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers