Effects of TNF-alpha or mmLDL on PAI-1 expression in human umbilical vein endothelial cells / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To demonstrate the changes of PAI-1 activity and mRNA expressions induced by tumor necrosis factor alpha (TNF-alpha) or minimally modified low-density lipoprotein (mmLDL) in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>The PAI-1 activity in HUVECs culture medium was measured by chromogenic assay. The PAI-1 mRNA expressions were determined by Northern blot. The mitogen-activated protein kinase-kinase (MAPKK) inhibitor and protein kinase C (PKC) inhibitor were used to intervene the inductions by TNF-alpha or mmLDL.</p><p><b>RESULTS</b>The PAI-1 activity and mRNA level were increased when HUVECs were exposed to TNF-alpha or mmLDL. The MAPKK inhibitor (PD98059, 60 mumol/L) could markedly inhibit PAI-1 activity and mRNA expression induced by TNF-alpha (100 U/ml) or mmLDL (50 micrograms/ml). But Staurosporine (10 nmol/L) and H7 (15 mumol/L), which were the PKC inhibitors, had no significant inhibition effect.</p><p><b>CONCLUSIONS</b>(1) TNF-alpha or mmLDL could induce PAI-1 activity and mRNA expression in HUVECs. (2) Increase of PAI-1 activity induced by TNF-alpha and mmLDL was related to its mRNA expression. (3) The MAPK pathway may play a role in PAI-1 expression induced by TNF-alpha or mmLDL.</p>