THE RELEASE OF 15-HYDROXYEICOSATETRAENOIC ACID BY HUMAN PLACENTAL TROPHOBLAST IS INCREASED IN PREECLAMPSIA

OBJECTIVE: We tested the hypothesis that trophoblast produces 15-hydro xyeicosatetraenoic acid, and its level is elevated in trophoblast from preeclamptic women compared with normal. We also used selective enzym atic inhibitors to determine the relative contributions of 15-lipoxyge nase and the two isozymes of prostaglandin H synthase to 15-hydroxyeic osatetraenoic acid levels. STUDY DESIGN: Cytotrophoblasts isolated fro m placentas of normal or preeclamptic women were cultured in the prese nce or absence of enzyme inhibitors. Media levels of 15-hydroxyeicosat etraenoic acid were measured by radioimmunoassay. RESULTS: When compar ed with normal pregnancies, cytotrophoblasts from preeclamptic pregnan cies released up to fivefold higher levels of 15-hydroxyeicosatetraeno ic acid. Aspirin, an inhibitor of both the prostaglandin H synthase-l and prostaglandin H synthase-2 isozymes, and nordihydroguaiaretic acid , a selective inhibitor of lipoxygenases, both significantly inhibited 15-hydroxyeicosatetraenoic acid production. In contrast, the selectiv e prostaglandin H synthase-2 inhibitor NS-398 had no effect on 15-hydr oxyeicosatetraenoic acid release in the absence of aspirin, but NS-398 reduced 15-hydroxyeicosatetraenoic acid levels in normal trophoblast pretreated with aspirin. CONCLUSIONS: The data indicate that 15-hydrox yeicosatetraenoic acid is produced in trophoblasts and its release by cytotrophoblasts is higher in preeclamptic pregnancies compared with n ormal controls. Both lipoxygenase and prostaglandin H synthase contrib ute to 15-hydroxyeicosatetraenoic acid production, and aspirin reduces 15-hydroxyeicosatetraenoic acid secretion. We suggest 15-hyroxyeicosa tetraenoic acid plays a role in the oxidation of lipoproteins and the endothelial damage characteristic of preeclampsia.