Oxidized low density lipoprotein inhibits prostacyclin generation by rat aorta in vitro: a key role of lysolecithin.

The objective of this study was to examine the effect of oxLDL on prostacyclin (PGI2) generation by rat aortic segments and to see whether the lipid fraction of oxLDL or its components are responsible for that effect. We also tested if antioxidants have any protective role. LDL oxidized by copper was characterized by higher TBARS, conjugated diene, lysophosphatidylcholine (lyso PC), oxysterols and less polyunsaturated fatty acids (PUFA) than nLDL. Preincubation of aortas with oxLDL caused a significant inhibition of PGI2 generation compared to aortas preincubated with nLDL or buffer only. The percent inhibition was dependent on the concentration of oxLDL. Most of the inhibitory effect of oxLDL resided in its lipid moiety while the lipid fraction of nLDL, as well as native LDL had no effect. Preincubation of aortas with 10 microg/ml of 7-ketocholesterol the major oxysterol in oxLDL reduced the amount of PGI2 generated by aorta at all times tested; however that decrease did not reach a significant level. Aortas preincubated with 10 microg/ml of lyso PC showed a 21-36% inhibition of PGI2 generation which was comparable to the inhibition produced by preincubating the aortas with 50 microg protein/ml of oxLDL (containing about 7.5 microg lyso PC). This indicated that most of the inhibitory effect of oxLDL was due to its lyso PC. The small molecular weight fraction (< 10 kDa) with a high level of TBARS (TBARS solution) also significantly decreased the PGI2 generation by aorta. Addition of superoxide dismutase (SOD) + catalase or vitamin E simultaneously with oxLDL or TBARS solution in the preincubation medium did not reverse their inhibitory effects. This indicated that oxygen free radicals are not a contributing factor to the inhibitory effect of oxLDL but lyso PC and the lipid peroxides and probably other components already present within oxLDL are the important inhibitors.