[Effects of TNF-alpha or mmLDL on PAI-1 expression in human umbilical vein endothelial cells].
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
(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.
Li
Xiao-dong
XD
Department of Pathophysiology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Zu
Shu-yu
SY
Zhu
Guang-jin
GJ
D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases