Comparison of the effects of O2*-/HO* free radical- and copper ions-oxidized LDL or lipoprotein(a) on the endothelial cell releases of tissue plasminogen activator and plasminogen activator inhibitor-1.
We investigated the effects of low density-lipoproteins (LDL) and lipoprotein(a) [Lp(a)] oxidized by O2*-/HO* free radicals generated by gamma radiolysis of water, on the release of tissue Plasminogen Activator (tPA) and of its main inhibitor Plaminogen Activator Inhibitor-1 (PAI-1) by human umbilical vein endothelial cells (HUVEC). These effects were compared to those of lipoproteins issued from the same preparations but oxidized by the classical copper ions procedure. The results showed that O2*-/HO* free radical oxidized LDL and Lp(a) led to a dramatic decrease of PAI-1 release but did not affect tPA release, whereas copper oxidation of lipoproteins resulted in an increase in PAI-1 release and a decrease in tPA release. Chemical analysis revealed that O2*-/HO* free radical oxidized lipoproteins exhibited very much lower levels of phosphatidylcholine hydroperoxides, lysophosphatidylcholine and oxysterols (7-ketocholesterol, 7beta-hydroxycholesterol, 5,6beta-epoxycholesterol) than copper oxidized LDL. Thus, the discordant effects of O2*-/HO* oxidized and copper oxidized LDL and Lp(a) on the endothelial releases of PAI-1 and tPA appeared to be due to qualitatively and/or quantitatively different formation of oxidized components by the two oxidation processes.
Beaudeux
J L
JL
Laboratoire de Biochimie Métabolique et Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France. jean-louis.beaudeux@psl.ap-hop-paris.fr
Therond
P
P
Bonnefont-Rousselot
D
D
Gardes-Albert
M
M
Legrand
A
A
Delattre
J
J
Peynet
J
J
D003300:Copper / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism* / Q000528:radiation effects; D007477:Ions; D007653:Ketocholesterols / Q000032:analysis; D017270:Lipoprotein(a) / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000032:analysis; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism* / Q000528:radiation effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014471:Umbilical Veins
D007477:Ions; D007653:Ketocholesterols; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D017395:Plasminogen Activator Inhibitor 1; C099252:oxidized low density lipoprotein; C057590:phosphatidylcholine hydroperoxide; D013481:Superoxides; D017665:Hydroxyl Radical; D003300:Copper; D010959:Tissue Plasminogen Activator