In vivo studies have demonstrated a strong positive correlation between plasma very low density lipoprotein (VLDL) triglyceride 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. It could be speculated that fatty acids derived from VLDL triglycerides are the actual mediators, resulting in an enhanced secretion of PAI-1. In the present study, we have analyzed the effects of both saturated and unsaturated fatty acids on PAI-1 expression and secretion by endothelial cells. Addition of 0 to 50 micromol/L of either palmitic acid or stearic acid had no effect on PAI-1 secretion from human umbilical vein endothelial cells or EA. hy926 cells. In contrast, addition of oleic acid, linoleic acid, linolenic acid, and eicosapentaenoic acid resulted in a significant increase in PAI-1 secretion from both cell types. Northern blot analysis of PAI-1 mRNA levels was in agreement with these findings. Transfection experiments demonstrated that addition of linolenic acid and eicosapentaenoic acid significantly increased PAI-1 transcription. The fatty acid response region was localized to a previously described VLDL-inducible region of the PAI-1 promoter. Electromobility shift assays 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 involve fatty acid oxidation to any significant extent. 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.

Unsaturated fatty acids increase plasminogen activator inhibitor-1 expression in endothelial cells / L. Nilsson, C. Banfi, U. Diczfalusy, E. Tremoli, A. Hamsten, P. Eriksson. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 18:11(1998 Nov), pp. 1679-1685. [10.1161/01.ATV.18.11.1679]

Unsaturated fatty acids increase plasminogen activator inhibitor-1 expression in endothelial cells

C. Banfi
Secondo
;
E. Tremoli;
1998-11

Abstract

In vivo studies have demonstrated a strong positive correlation between plasma very low density lipoprotein (VLDL) triglyceride 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. It could be speculated that fatty acids derived from VLDL triglycerides are the actual mediators, resulting in an enhanced secretion of PAI-1. In the present study, we have analyzed the effects of both saturated and unsaturated fatty acids on PAI-1 expression and secretion by endothelial cells. Addition of 0 to 50 micromol/L of either palmitic acid or stearic acid had no effect on PAI-1 secretion from human umbilical vein endothelial cells or EA. hy926 cells. In contrast, addition of oleic acid, linoleic acid, linolenic acid, and eicosapentaenoic acid resulted in a significant increase in PAI-1 secretion from both cell types. Northern blot analysis of PAI-1 mRNA levels was in agreement with these findings. Transfection experiments demonstrated that addition of linolenic acid and eicosapentaenoic acid significantly increased PAI-1 transcription. The fatty acid response region was localized to a previously described VLDL-inducible region of the PAI-1 promoter. Electromobility shift assays 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 involve fatty acid oxidation to any significant extent. 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.
RNA, Messenger; Promoter Regions, Genetic; Fatty Acids, Unsaturated; Transcription Factors; Cells, Cultured; Humans; Lipoproteins, VLDL; Plasminogen Activator Inhibitor 1; Fatty Acids; Transcription, Genetic; Protein Binding; Endothelium, Vascular
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
1679.full.pdf

accesso solo dalla rete interna

Tipologia: Publisher's version/PDF
Dimensione 624.31 kB
Formato Adobe PDF
624.31 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/187796
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 87
  • ???jsp.display-item.citation.isi??? 83
social impact