Stimulatory effect of unsaturated fatty acids on the level of plasminogen activator inhibitor-1 mRNA in cultured human endothelial cells.
To determine whether unsaturated fatty acids induce changes in the mRNA level of plasminogen activator inhibitor type-1 (PAI-1), Northern analyses were performed on human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells that were treated with two common fatty acids. Supplementation of cultured HUVEC with docosahexanoic acid (DHA) or with dihomogamma linolenic acid (DGLA), resulted in a concentration dependent, specific increase of the PAI-1 transcript levels, which was detectable within 2 h. DHA and DGLA treatment of smooth muscle cells did not result in changes in the PAI-1 mRNA levels. Homology search of the upstream regulatory region of the PAI-1 gene sequences identified a consensus nucleotide sequence for a fatty acid-responsive element. Our results indicate that unsaturated fatty acids selectively increase PAI-1 mRNA levels in endothelial cells, the primary source of circulating PAI-1 in vivo.
Karikó
K
K
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6060.
Rosenbaum
H
H
Kuo
A
A
Zurier
R B
RB
Barnathan
E S
ES
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D016384:Consensus Sequence / Q000235:genetics; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D017965:gamma-Linolenic Acid