Comparison of the effects of O-2(center dot-)/HO center dot 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 lipoprote in(a) [Lp(a)] oxidized by O-2(.-)/HO. free radicals generated by gamma radi olysis of water, on the release of tissue Plasminogen Activator (tPA) and o f its main inhibitor Plaminogen Activator Inhibitor-1 (PAI-1) by human umbi lical vein endothelial cells (HUVEC). These effects were compared to those of lipoproteins issued from the same preparations but oxidized by the class ical copper ions procedure. The results showed that O-2(.-)/HO. free radica l oxidized LDL and Lp(a) led to a dramatic decrease of PAI-1 release but di d not affect tPA release, whereas copper oxidation of lipoproteins resulted in an increase in PAI-1 release and a decrease in tPA release. Chemical an alysis revealed that O-2(.-)/HO. free radical oxidized lipoproteins exhibit ed very much lower levels of phosphatidylcholine hydroperoxides, lysophosph atidylcholine and oxysterols (7-ketocholesterol, 7 beta -hydroxycholesterol , 5,6 beta -epoxycholesterol) than copper oxidized LDL. Thus, the discordan t effects Of O-2(.-)/HO. oxidized and copper oxidized LDL and Lp(a) on the endothelial releases of PAI-1 and tPA appeared to be due to qualitatively a nd/or quantitatively different formation of oxidized components by the two oxidation processes. (C) 2001 Elsevier Science Inc. All rights reserved.