Document Detail

The release of 15-hydroxyeicosatetraenoic acid by human placental trophoblast is increased in preeclampsia.
MedLine Citation:
PMID:  9465803     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: We tested the hypothesis that trophoblast produces 15-hydroxyeicosatetraenoic 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. CONCLUSIONS: The data indicate that 15-hydroxyeicosatetraenoic 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-hydroxyeicosatetraenoic 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.
R D Johnson; K L Polakoski; X Huang; Y Sadovsky; D M Nelson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  178     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-03-06     Completed Date:  1998-03-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  54-8     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynecology, St. Louis, MO 63110-1094, USA.
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MeSH Terms
Aspirin / pharmacology
Cells, Cultured
Cyclooxygenase Inhibitors / pharmacology
Hydroxyeicosatetraenoic Acids / metabolism*
Isoenzymes / antagonists & inhibitors,  physiology
Lipoxygenase / physiology
Lipoxygenase Inhibitors / pharmacology
Nordihydroguaiaretic Acid / pharmacology
Pre-Eclampsia / metabolism*,  pathology
Prostaglandin-Endoperoxide Synthases / physiology
Time Factors
Trophoblasts / cytology,  metabolism*,  pathology
Grant Support
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Hydroxyeicosatetraenoic Acids; 0/Isoenzymes; 0/Lipoxygenase Inhibitors; 50-78-2/Aspirin; 500-38-9/Nordihydroguaiaretic Acid; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid; EC; EC Synthases

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