To examine the effect of oxidized low density lipoprotein (oxLDL) on prostacyclin (PGI2) generation by rat aorta in vitro and whether high density lipoprotein (HDL) has any protective effect against the inhibition of PGI2 generation induced by oxLDL is the objective of this study. Preincubation of aortas with oxLDL resulted in significant inhibition of PGI2 generation compared to preincubation with normal low density lipoprotein (nLDL) or buffer only. The inhibitory effect of oxLDL resided in its lipid moiety while the lipid fraction of nLDL showed no effect. Aortas preincubated with 10 microg/ml of lyso phosphatidycholine (lyso PC) also showed 30% inhibition of PGI2 generation, indicating that lyso PC was among the lipid components of oxLDL which inhibited PGI2 generation. Preincubation of aortas with a mixture of HDL and oxLDL at a ratio of 10:1 showed a significant recovery of PGI2 generation compared to aortas preincubated with only oxLDL, indicating a protective role for HDL. When HDL was incubated with oxLDL the transfer of lyso PC from oxLDL to HDL suggested that HDL trapped lyso PC from oxLDL thus preventing it from acting on the aorta. However, when a mixture of HDL and oxLDL at a ratio of 3:1 was preincubated with aortas, no protective effect of HDL was observed. Preincubation of aortas with a mixture of HDL plus oxLDL at a ratio of 8:1, which was incubated for 1 h at 37 degrees C, produced significantly less PGI2 than aortas preincubated only with oxLDL, indicating that HDL under these conditions was not protective but even enhanced the inhibitory effect of oxLDL. Similarly, aortas preincubated with HDL plus whole oxLDL (at a ratio of 10:1); containing all the small molecular weight oxidation products and characterized by high levels of thiobarbituric acid reactive substance (TBARS) and lipid hydroperoxides; produced significantly less PGI2 than aortas preincubated with whole oxLDL. These results were evaluated in light of possible modification of HDL by oxLDL and its lipid oxidation products such as aldehydes and lipid peroxides. The modified HDL can add more lipid peroxides and increase the effectiveness of lipid peroxides originally present in oxLDL.
Animals Aorta