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PPARalpha activators inhibit tissue factor expression and activity in human monocytes.

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Peroxisome proliferator-activated receptor-alpha (PPARalpha) activators reduce tissue factor (TF) expression and activity in human monocytes. This finding suggests a potential therapeutic strategy for reducing thrombogenicity in atherosclerotic lesions.

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Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Pharmacology

Background:

  • Tissue factor (TF) on monocytes/macrophages initiates thrombus formation in acute coronary syndromes.
  • Peroxisome proliferator-activated receptor-alpha (PPARalpha) regulates gene expression.
  • PPARalpha activators may reduce TF activity in patients.

Purpose of the Study:

  • To investigate if PPARalpha activators can limit TF responses in human monocytic cells.
  • To explore the mechanism by which PPARalpha activators affect TF expression.

Main Methods:

  • Human monocytes and macrophages were treated with PPARalpha activators (WY14643, ETYA).
  • Lipopolysaccharide (LPS) was used to induce TF activity and expression.
  • TF activity, protein, mRNA, and promoter activity were measured.
  • Nuclear factor-kappaB (NF-κB) binding and activity were assessed.

Main Results:

  • PPARalpha activators significantly reduced LPS-induced TF activity and expression in monocytes/macrophages.
  • PPARgamma activators did not show similar effects.
  • WY14643 decreased tumor necrosis factor-alpha protein and inhibited LPS-induced TF promoter activity, likely via NF-κB inhibition.

Conclusions:

  • PPARalpha activators effectively reduce TF expression and activity in human monocytes/macrophages.
  • These findings suggest a potential role for PPARalpha activators in reducing atherosclerotic lesion thrombogenicity.
  • The data offer insights into how PPARalpha-activating compounds may impact atherothrombosis.