High-density lipoprotein inhibits the synthesis of platelet-activating factor in human vascular endothelial cells.
The regulation of platelet-activating factor (PAF) synthesis by serum lipoproteins was investigated in human umbilical vein endothelial cells. High-density lipoprotein (HDL) inhibited PAF synthesis in agonist (thrombin, histamine, and A23187)-stimulated endothelial cells, that was determined by incorporation of [3H]acetate into PAF and by bioassay. The inhibition by HDL was increased in a concentration-dependent manner, but was reversed as the concentration of thrombin increased. HDL did not affect the time course of PAF production. HDL lipids suppressed the PAF production to a lesser extent than HDL. The reduction of PAF accumulation in HDL, did not result from degradation of PAF but inhibition of PAF synthesis, which was mainly mediated via the blockade of acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activation. HDL did not prevent the release of [3H]arachidonic acid in thrombin-stimulated endothelial cells. The binding of 125I-HDL to endothelial cells and its uptake were not enhanced by thrombin stimulation. These results demonstrate that HDL may inhibit the activation of acetyltransferase by thrombin at the cell surface. This observation may explain a part of mechanism of HDL action.
Sugatani
J
J
Department of Medical Chemistry, Kansai Medical University, Osaka, Japan.
Miwa
M
M
Komiyama
Y
Y
Ito
S
S
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000001:Calcimycin; D006632:Histamine; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D013917:Thrombin