Activities of phospholipase A2, cyclooxygenase, and PGI2 synthase of umbilical venous endothelial cells in preeclamptic women.
To elucidate the cause of low prostacyclin (PGI2) production in severe preeclampsia (PE), we studied the activities of phospholipase A2, cyclooxygenase, and PGI2 synthase in umbilical venous endothelial cells obtained from healthy pregnant women and from patients with mild or severe PE. Umbilical venous endothelial cells homogenized in a buffer solution were analysed by calculating the apparent Vmax (mean +/- SEM: p mol/min mg protein) and Km (mean +/- SEM: microM) values for phospholipase A2 activity by the release of arachidonic acid from phosphatidylcholine, for the activity of a complex of cyclooxygenase and PGI2 synthase by the conversion of arachidonic acid to PGI2, and the activity of PGI2 synthase by conversion of PGH2 to PGI2. The phospholipase A2 activity of normal-pregnancy cells (Vmax: 17.0 +/- 2.7 Km: 0.26 +/- 0.04) (n = 10) significantly exceeded that of cells from women with either mild PE (5.8 +/- 0.5, 0.12 +/- 0.02) (n = 4) or severe PE (6.3 +/- 2.0, 0.08 +/- 0.03) (n = 5). The apparent combined activity of cyclooxygenase and PGI2 synthase in mild PE (552 +/- 142, 0.29 +/- 0.07) (n = 8) significantly exceeded that of a normal pregnancy (176 +/- 42, 0.76 +/- 0.25) (n = 7), whereas that in severe PE (326 +/- 36, 3.26 +/- 0.78) (n = 3) was significantly lower than that of a normal pregnancy. PGI2 synthase activity in mild PE (305 +/- 50, 0.12 +/- 0.07) (n = 4) exceeded that of a normal pregnancy (220 +/- 45, 0.13 +/- 0.06) (n = 5), whereas that in severe PE (55 +/- 12, 0.16 +/- 0.04) (n = 3) was lower than that of a normal pregnancy. The phospholipase A2 activity in cells of normal pregnant women exceeded that of cells of women with mild or severe PE. The combined activity of cyclooxygenase and PGI2 synthase in a normal pregnancy was lower than in mild PE, but higher than in severe PE. Similar results were found for PGI2 synthase activity; in normal pregnancy the activity was less than in mild PE, but higher than in severe PE.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical School, Japan.
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Seki
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Takeda
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Kinoshita
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Satoh
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology
D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase