Effects of PGI(2) and analogues (taprostene, iloprost) on oxidation of native and glycated LDL

Oxidation and glycation of low-density lipoprotein (LDL) has been claimed t o play a central role in the pathogenesis of atherosclerosis. Therefore, th e inhibition of this processes is of major therapeutic importance. In the p resent paper the influence of prostaglandin (PG)I-2, and its stable analogu es taprostene and iloprost on copper-induced oxidation of native, glycated and glycoxidated LDL was investigated. The results show, that the most pron ounced effect on inhibition of native LDL-oxidation was obtained by taprost ene in the whole concentration range tested (0.2 mu g-10 mu g/ml) reaching a maximal inhibition of 95% at 10 mu g/ml. Examining glycoxidated LDL the i nhibitory effect on oxidation was less pronounced reaching only about 10%. In case of glycated LDL, however, no significant inhibitory effect on oxida tion was seen. Iloprost was effective as inhibitory agent against oxidation of native LDL at concentrations of 10 and 20 mu g/ml, showing a maximal in hibition of 86% at a concentration of 201 mu g/ml. Iloprost was ineffective on oxidation of glycated and glycoxidated LDL. Examining the extremely sho rt-lived PGI(2) itself, no significant inhibitory effect on oxidation of na tive, glycated or glycoxidated LDL, however, was seen. This finding might b e of relevance for patients with diabetes mellitus, showing a decreased end ogenous PGI(2)-production in particular those with bad metabolic control an d high concentrations of circulating advanced glycosylation end products (A GEs).