The release of 15-hydroxyeicosatetraenoic acid by human placental trophoblast is increased in preeclampsia

R. D. Johnson, K. L. Polakoski, X. Huang, Y. Sadovsky, D. M. Nelson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

OBJECTIVE: We tested the hypothesis that trophoblast produces 15- hyroxyelcosatetraenoic acid, and its level is elevated in trophoblast from preeclamptic women compared with normal. We also used selective enzymatic inhibitors to determine the relative contributions of 15-lipoxygenase and the two isozymes of prostaglandin H synthase to 15-hydroxyeicosatetraenoic acid levels. STUDY DESIGN: Cytotrophoblasts isolated from placentas of normal or preeclamptic women were cultured in the presence or absence of enzyme inhibitors. Media levels of 15-hydroxyeicosatetraenoic acid were measured by radioimmunoassay. RESULTS: When compared with normal pregnancies, cytotrophoblasts from preeclamptic pregnancies released up to fivefold higher levels of 15-hydroxyeicosatetraenoic acid. Aspirin, an inhibitor of both the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes, and nordihydroguaiaretic acid, a selective inhibitor of lipoxygenases, both significantly inhibited 15-hydroxyeicosatetraenoic acid production. In contrast, the selective prostaglandin H synthase-2 inhibitor NS-398 had no effect on 15-hydroxyeicosatetraenoic acid release in the absence of aspirin, but NS-398 reduced 15-hydroxyeicosatetraenoic acid levels in normal trophoblast pretreated with aspirin. CONCLUSION: The data indicate that 15- hydroxyeicosatetreanoic acid is produced in trophoblasts and its release by cytotrophoblasts is higher in preeclamptic pregnancies compared with normal controls. Both lipoxygenase and prostaglandin H synthase contribute to 15- hydroxyeicosatraenoic acid production, and aspirin reduces 15- hydroxyeicosatetraenoic acid secretion. We suggest 15- hydroxyeicosatetraenoic acid plays a role in the oxidation of lipoproteins and the endothelial damage characteristic of preeclampsia.

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalAmerican journal of obstetrics and gynecology
Volume178
Issue number1 I
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Keywords

  • 15-HETE
  • Placenta
  • Preeclampsia
  • Trophoblast

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