Effects of lipid peroxides on prostacyclin and thromboxane generation in hypercholesterolemic rabbits

Rabbits fed an atherogenic diet for 60 days resulted in high levels of plasma lipid peroxides as well as extreme hypercholesterolemia. Both levels stayed high until 35 days after the atherogenic diet stopped. At the same time, plasma PGI2 level was remarkably decreased while TXA2 and platelet aggregability were increased. Atherosclerotic aortas contain high levels of lipid peroxides associated with decreased PGI2 and increased TXA2 generation. Atherosclerotic plaques had the highest level of lipid peroxides and TXA2 while PGI2 production was the least, as compared with nonplaque tissue of the same artery and the normal arteries. The condition of normal arteries was just the reverse. There was a negative correlation between lipid peroxides and prostacyclin production, and a positive correlation between lipid peroxides and TXA2, in both plasma and aorta of rabbits. These results suggest that there is a close correlation between atherosclerosis, elevated lipid peroxides, and disturbances in PGI2/TXA2 balances.