Prostaglandin E2 biosynthesis and effect in pigeon aorta. Possible role in atherogenesis

Abstract

This study for the first time examines the biosynthesis and effect of prostaglandin E2 (PGE2) in aorta during genetic atherosclerosis. Biosynthesis of PGE2 from [1-14C]arachidonic acid was investigated in the aorta of spontaneously atherosclerosis-susceptible White Carneau pigeons and was compared with that of the atherosclerosis-resistant Show Racer breed. Most of the PGE2 synthetase activity was located in the microsomes. The synthesis was linear up to an hour and was optimal at pH 7.4. The formation of PGE2 in the aorta in the White Carneau pigeons was significantly higher (P less than 0.01) than that in age-matched Show Racer pigeons. In vitro PGE2 strongly inhibited the cholesteryl ester hydrolase activity (51.6% inhibition at 4 X 10(-7) M concentration) in the supernatant fraction of the aorta. On the basis of (1) the increased formation of PGE2 in the aorta of atherosclerosis-susceptible pigeons and (2) its effect on specific enzymes that control cholesteryl ester concentration in aorta, it is hypothesized that PGE2 synthesized at a higher rate in damaged aorta has a significant role in cholesteryl ester accumulation during atherogenesis.