The effect of cholesterol oxidation products on human platelet aggregation.
The cholesterol oxidation products (oxysterols) cholest-3,5-diene-7-one, cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol (cholesterol 5 alpha-epoxide), cholestan-5 beta, 6 beta-epoxy-3 beta-ol (cholesterol 5 beta-epoxide), cholest-5-ene-3 beta-ol-7-one (7-ketocholesterol), cholest-5-ene-3 beta, 7 alpha-diol (7 alpha-hydroxycholesterol), cholestan-3 beta, 5 alpha, 6 beta-triol (cholestane triol), and cholest-5-ene-3 beta, 26-diol (27-hydroxycholesterol) potentiated platelet aggregation and increased thromboxane A2 formation in platelets challenged with thrombin, ADP or collagen. These effects were observed at oxysterol concentrations in the range 5-100 microM. Cholesterol 5 beta-epoxide and 7-ketocholesterol increased the mobilization of 3H-arachidonic acid from prelabelled platelet phospholipids in response to thrombin and collagen.
Selley
M L
ML
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Woden Valley Hospital, Garran, A.C.T., Australia.
McGuiness
J A
JA
Ardlie
N G
NG
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry*; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects*; D013261:Sterols / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D013261:Sterols; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D002784:Cholesterol; D013917:Thrombin