Effect of retinoic acid on the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cells.
The synthesis of plasminogen activators and inhibitors in endothelial cells is highly regulated by hormones, drugs and growth factors. The present study evaluates the effect of retinoic acid on the synthesis of tissue-type plasminogen activator (t-PA) and of plasminogen activator inhibitor-1 (PAI-1) by cultured human umbilical vein endothelial cells (HUVEC). Retinoic acid produced a time- and concentration-dependent increase in the secretion of t-PA-related antigen but not of PAI-1 related antigen into the culture medium. A maximal sevenfold increase of t-PA antigen after 24 h was observed with 10 microM and a half-maximal increase with 0.1 microM retinoic acid. Retinoic acid induced a time-dependent increase of the t-PA mRNA, with a maximum at 8 h and returning to normal at 24 h. The protein kinase inhibitor H7 decreased the t-PA antigen induced by both retinoic acid and phorbol 12-myristate 13-acetate. These results suggest that treatment of HUVEC with retinoic acid increases t-PA production by a pathway which, at some level, involves protein kinases. Thus, retinoic acid induces t-PA synthesis in the absence of altered PAI-1 synthesis, which may enhance the fibrinolytic potential of the endothelium.
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
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Thompson
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Nelles
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002478:Cells, Cultured; D004224:Diterpenes; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D015336:Molecular Probe Techniques; D010879:Piperazines / Q000494:pharmacology; D015849:Plasminogen Inactivators / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000187:drug effects; D000084562:Retinyl Esters; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology
D004224:Diterpenes; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010879:Piperazines; D015849:Plasminogen Inactivators; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D010959:Tissue Plasminogen Activator