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.
- Author:
Yong-Jun CAO
1
;
Yan-Hua WU
;
Chun-Feng LIU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Arteriosclerosis; metabolism; pathology; Cells, Cultured; Coculture Techniques; Endothelial Cells; metabolism; Fibrin; metabolism; Fibrin Fibrinogen Degradation Products; metabolism; Fibrinogen; metabolism; Humans; Plasminogen Activator Inhibitor 1; metabolism; RNA, Messenger; metabolism; Rabbits; Tissue Plasminogen Activator; metabolism
- From: Chinese Journal of Cardiology 2008;36(1):62-67
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSFg, 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.
RESULTStPA 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.
CONCLUSIONFg, Fb and FDPs play important roles in the pathogenesis of atherosclerosis by modulating the expression of tPA and PAI-1 of endothelial and SMCs.