Polyunsaturated fatty acids influence prostanoid synthesis in vascular endothelial cells under hypoxia and reoxygenation.
We studied the influence of membrane polyunsaturated fatty acids (PUFA) on prostanoid metabolism in the vascular endothelium, in pathophysiological conditions. Two models of cultured endothelial cells were used, from bovine aorta (BAEC) and human umbilical vein (HUVEC). In physiological conditions, the main prostanoids were prostacyclin and PGE2 in the BAEC and prostacyclin and PGF2 alpha in the HUVEC. Reoxygenation (2.5 hours) but not hypoxia (2.5 hours) enhanced prostanoid synthesis in both models. Cell enrichment with arachidonic acid (AA, n-6 cells) increased both AA and C22:4 n-6 and decreased n-3 PUFAs in the phospholipids. Conversely enrichment with eicosapentaenoic and docosahexaenoic acids (EPA and DHA, n-3 cells) increased the n-3 PUFAs and decreased the n-6 PUFAs. The BAEC incorporated more PUFA in the phospholipids than the HUVEC. Moreover in the n-3 cells, EPA incorporation was higher than that of DHA. Increasing AA increased the production of both prostacyclin and PGF2 alpha by the BAEC and only that of PGF2 alpha by the HUVEC. Increasing n-3 PUFA decreased the release of PGE2 and TxA2 by the BAEC and only that of prostacyclin by the HUVEC. In the n-6 cells, hypoxia became a stimulus for prostanoid production and the stimulating effect of reoxygenation was reinforced in the HUVEC whereas it was abolished in the BAEC. N-3 PUFA blocked the reoxygenation-stimulated production. These results suggest a strong importance of dietary PUFA in the response of vascular endothelium to pathological conditions.
Lipides Membranaires et Fonctions Cardiovasculaires, INRA, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
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F
Oudot
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C
Cordelet
J P
JP
Sergiel
A
A
Grynberg
D000818:Animals; D001011:Aorta; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D015687:Cell Hypoxia; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010100:Oxygen / Q000008:administration & dosage*; D011453:Prostaglandins / Q000096:biosynthesis*; D014471:Umbilical Veins
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone; D010100:Oxygen