STIMULATORY EFFECT OF UNSATURATED FATTY-ACIDS ON THE LEVEL OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 MESSENGER-RNA IN CULTURED HUMAN ENDOTHELIAL-CELLS

To determine whether unsaturated fatty acids induce changes in the mRN A level of plasminogen activator inhibitor type-1 (PAI-1). Northern an alyses were performed on human umbilical vein endothelial cells (HUVEC ) and vascular smooth muscle cells that were treated with two common f atty acids. Supplementation of cultured HUVEC with docosahexanoic acid (DHA) or with dihomogamma linolenic acid (DGLA), resulted in a concen tration dependent, specific increase of the PAI-1 transcript levels, w hich was detectable within 2 h. DHA and DGLA treatment of smooth muscl e cells did not result in changes in the PAI-1 mRNA levels. Homology s earch of the upstream regulatory region of the PAI-1 gene sequences id entified a consensus nucleotide sequence for a fatty acid-responsive e lement. 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.