Abstract

To investigate the regulatory role of RhoA/Rho kinase in the effects of fluvastatin (Flu) on the tumor necrosis factor-α (TNF-α) induced expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVECs) which may provide basis for the prevention of arterial thrombosis, HUVECs in logarithmic phase were divided into TNF-α group, Flu group and TNF-α+Flu group. enzyme-linked immunosorbent assay (ELISA), real time polymerase chain reaction (RT-PCR) and western blot assay were employed to detect the content of TF, messenger ribonucleic acid (mRNA) expression of TF and protein expressions of TF and activated RhoA, respectively. Then, Angiotensin II (Ang II) and Y27632 were used to treat these cells which were then divided into control group, TNF-α+Ang II group, AngII group, TNF-α group and TNF-α+Y27632 group. Western blot assay was performed to detect the protein expression of TF. After TNF-α treatment, the content and mRNA and protein expressions of TF were markedly increased when compared with the control group (P<0.05). However, the content and mRNA and protein expressions of TF in Flu group were significantly lower than those in TNF-α group (P<0.05). Our results showed TNF-α could induce TF expression in HUVECs and activate RhoA, which, however, were inhibited by Flu. Ang II treatment could increase the TNF-α induced TF expression in HUVECs which however was inhibited Y27632. Flu could effectively inhibit the TNF-α induced protein and mRNA expressions of TF in HUVECs in which RhoA/Rho signaling pathway may play an important role.

Key words: Tissue factor, endothelial cells, fluvastatin, RhoA/Rho kinase, angiotensin II, Y27632.