Alteration in prostacyclin and prostaglandin E2 production. Correlation with changes in human aortic atherosclerotic disease.

Abstract

Prostacyclin (PGI2) and prostaglandin E2 (PGE2) production was investigated in human aortas (five controls and 27 with atherosclerotic lesions). The specific activities of PGI2 and PGE2 synthetase were studied using radioimmunoassays of PGE2 and 6-keto-PGE1 alpha of aortic microsomes incubated in the presence of additional substrate and cofactors. The atherosclerotic lesions were examined under the light microscope and were classified as Stage 1 when the disease was restricted to the intima and as Stages 2 and 3 when there were moderate or advanced lesions. Prostaglandin production for the control group (n = 5), Stage 1 (n = 7), Stage 2 (n = 10), and Stage 3 (n = 10) were as follows: 454 +/- 15, 162 +/- 81, 92 +/- 90, and 65 +/- 61 pmol 6-K-PGF1 alpha/50 mg protein/10 minutes; and 15 +/- 12, 399 +/- 406, 227 +/- 174, and 366 +/- 362 pmol PGE2/50 mg protein/10 minutes (mean +/- SD) respectively. We conclude that: 1) In normal aortas, PGE2 production was low, while PGI2 synthesis activity was elevated. The reverse situation was observed in aortas with atherosclerosis lesions (p less than 0.05). 2) There was an inverse relationship between PGE2 and PGI1 production (p less than 0.05). 3) There was a direct histologic relationship between lower PGI2 production and atherosclerosis progression. A decided decline in 6-K-PGF1 alpha production was detected in aortas in the early stages (65% of control values). 4) By contrast, a progressive increase in PGE2 production was found in Stage 2 and Stage 3 groups (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)