Regulation by nitric oxide of endotoxin-induced tissue factor and plasminogen activator inhibitor-1 in endothelial cells.
The increase in nitric oxide (NO) production in lipopolysaccharide (LPS)-induced sepsis is thought to contribute to the development of shock. However, NO could also play an antithrombotic role. Little is known about the modulating effect of NO on the endothelial overexpression and production of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) occurring in endotoxemia. We analyzed the effect of N(G)-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthases, and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a NO donor, on the expression and synthesis of TF and PAI-1 by LPS-challenged human umbilical vein endothelial cells (HUVEC): L-NAME enhanced the increase in TF mRNA and antigen levels (P <0.05) observed in LPS-treated HUVEC; SNAP down-regulated the LPS-induced TF increment (p <0.05). However, no effects of NO on regulation of the LPS-dependent increase in PAI-1 could be seen. Thus, NO could play an antithrombotic role in sepsis by down-regulating the endothelial overexpression and production of TF.
Pérez-Ruiz
Ana
A
Haematosis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain.
Montes
Ramón
R
Velasco
Francisco
F
López-Pedrera
Chary
C
Antonio Páramo
José
J
Orbe
Josune
J
Hermida
José
J
Rocha
Eduardo
E
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D013925:Thromboplastin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester