Unsaturated fatty acids increase PAI-1 expression in endothelial cells

L. Nilsson, C. Anfi, U. Diczfalusy, E. Tremoli, A. Hamsten, P. Eriksson

Research output: Contribution to journalArticlepeer-review


In vivo studies have demonstrated a strong positive correlation between plasma very low density lipoprotein (VLDL) triglycéride and plasma plasminogen activator inhibitor-1 (PAI-1) activity levels. Furthermore, VLDL has been shown to induce PAI-1 secretion from cultured endothelial cells. In contrast, no or variable effects on PAI-1 secretion have been reported for native low density lipoprotein (LDL). It could be speculated that fatty acids derived from VLDL triglycérides are the actual mediator, resulting in an enhanced secretion of PAI-1. In the present study we have elucidated the effects of both saturated and unsaturated fatty acids on PAI-1 expression and secretion by endothelial cells. Addition of either 0-50 jjM of palmitic acid or stearic acid had no effect on PAI-1 secretion from HUVEC or EA.hy926 cells. In contrast, addition of oleic acid, linoleic acid, linolenic acid and eicosapentanoic acid (EPA) resulted in a significant increase in PAI-1 secretion from both cell types. Northern blot analysis of PAI-1 mRNA levels were in agreement with these findings. Transfection experiments demonstrated that addition of linolenic acid and EPA significantly increased PAI-1 transcription. The fatty acid response region was localized to a previously described VLDL-inducible region of the PAI-1 promoter. EMS As demonstrated that unsaturated fatty acids induced the same complex as did VLDL whereas saturated fatty acids had no effect. Furthermore, it was demonstrated that the activation procedure did not to any significant extent involve fatty acid oxidation. In conclusion, the present study demonstrates that unsaturated fatty acids increase PAI-1 transcription and secretion by endothelial cells in vitro. The effect appears to be mediated by a previously described VLDL-inducible transcription factor.

Original languageEnglish
Pages (from-to)23
Number of pages1
JournalFibrinolysis and Proteolysis
Issue numberSUPPL. 1
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Hematology


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