PPARγ Activation in Human Endothelial Cells Increases Plasminogen Activator Inhibitor Type-1 Expression

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Abstract
—Plasminogen activator inhibitor type-1 (PAI-1) is a major physiological inhibitor of fibrinolysis, with its plasma levels correlating with the risk for myocardial infarction and venous thrombosis. The regulation of PAI-1 transcription by endothelial cells (ECs), a major source of PAI-1, remains incompletely understood. Adipocytes also produce PAI-1, suggesting possible common regulatory pathways between adipocytes and ECs. Peroxisomal proliferator-activated receptor-γ (PPAR)γ is a ligand-activated transcription factor that regulates gene expression in response to various mediators such as 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and oxidized linoleic acid (9- and 13-HODE). The present study tested the hypotheses that human ECs express PPARγ and that this transcriptional activator regulates PAI-1 expression in this cell type. We found that human ECs contain both PPARγ mRNA and protein. Immunohistochemistry of human carotid arteries also revealed the presence of PPARγ in ECs. Bovine ECs transfec...