Eicosapentaenoic acid suppresses basal and insulin-stimulated endothelin-1 production in human endothelial cells.
cis-Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are the major fatty acids contained in fish oil, and are known to affect the various physiological properties of cell membranes in humans. The present study investigated the effects of polyunsaturated fatty acids on endothelin-1 (ET-1) production in human umbilical vein endothelial cells (HUVECs) and on insulin activity. After addition of various concentrations of EPA, docosahexaenoic acid, arachidonic acid, or linoleic acid to a culture medium, the concentration of ET-1 was measured using ELISA, and that of ET-1 mRNA was determined by RT-PCR. The results showed that EPA had the strongest inhibitory effect (p<0.05) on both basal ET-1 production and ET-1 mRNA levels. In addition, insulin (1 micromol/l) markedly increased ET-1 production, and EPA also significantly decreased the effect induced by insulin. Pretreatment with Ca2+ chelator EGTA (1 mmol/l), NOS inhibitor L-NAME (300 micromol/l), or calmodulin antagonist W-7 (300 micromol/l) inhibited NO production by EPA (100 micromol/l), but these pretreatments had no effect on ET-1 production by EPA. These findings suggest that EPA reduces basal and insulin-enhanced ET-1 production by inhibiting ET-1 mRNA production. These effects of EPA may contribute to its vasorelaxant and anti-atherosclerotic effects.
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
Keigo
K
Chisaki
Yukichi
Y
Okuda
Seiji
S
Suzuki
Takashi
T
Miyauchi
Masaaki
M
Soma
Norio
N
Ohkoshi
Hirohito
H
Sone
Nobuhiro
N
Yamada
Toshiaki
T
Nakajima
D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D015118:Eicosapentaenoic Acid; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D002614:Chelating Agents; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D013449:Sulfonamides; D009569:Nitric Oxide; D004533:Egtazic Acid; C017967:W 7; D015118:Eicosapentaenoic Acid; D019331:NG-Nitroarginine Methyl Ester