[Effect of fibrinogen, fibrin and fibrin (ogen) degradation products on the tissue plasminogen activator and plasminogen activator inhibitor-1 expressions of vascular endothelial cells in coculture system].
OBJECTIVE
To investigate the effect of fibrinogen (Fg), fibrin (Fb) and fibrin (ogen) degradation products (FDPs) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) expressions of human umbilical vein endothelial cells (HUVECs) in coculture system.


METHODS
Fg, Fb and FDPs at various concentrations (0, 0.5, 1.5, 3.0, 4.5 and 6.0 g/L) were added to the transwell coculture system of HUVECs and smooth muscle cells (SMCs) for 24 hours. The expressions of tPA and PAI-1 at mRNA level were examined by RT-PCR and tPA and PAI-1 protein and activity were detected by ELISA and substrate chromogenic assays.


RESULTS
tPA expression was not affected by Fg. Fg at concentrations between 3.0 - 4.5 g/L significantly enhanced the mRNA expression, protein content and activity of PAI-1, while expression of PAI-1 was significantly inhibited by Fg at concentration of 6.0 g/L. Fb at concentrations between 3.0 - 4.5 g/L significantly up-regulated mRNA expression, increased protein content and down-regulated activity of tPA. Fb (1.5 - 4.5 g/L) also enhanced the mRNA expression, increased protein content and activity of PAI-1. FDPs at concentrations 3.0 - 6.0 g/L down-regulated the expression of tPA and FDPs at concentrations 1.5 - 6.0 g/L significantly enhanced PAI-1 mRNA expression.


CONCLUSIONS
Fg, Fb and FDPs play important roles in the pathogenesis of atherosclerosis by modulating the expression of tPA and PAI-1 of endothelial and SMCs.
Cao
Yong-Jun
YJ
Department of Neurology, Second Affiliated Hospital of Suzhou University, Suzhou 215004, China.
Wu
Yan-Hua
YH
Liu
Chun-Feng
CF
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D005337:Fibrin; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator