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.
Highlights
Studies have demonstrated that tissue factor (TF) is closely associated with the arterial thrombosi (Steffel et al, 2006; Wolfovitz, 2005)
The present study aimed to investigate the suppressive effects of fluvastatin (Flu) on the activity and protein and messenger ribonucleic acid expressions of TF as well as Rho activation in human umbilical vein endothelial cells (HUVECs) following tumor necrosis factor- (TNF- ) treatment in which Angiotensin II (Rho kinase agonist) and Y27632 (Rho kinase antagonist) were used
HUVECs were incubated with Flu at 0, 0.01, 0.1, 1, 10 or 100 mol/L for 6 h and with TNF
Summary
Studies have demonstrated that tissue factor (TF) is closely associated with the arterial thrombosi (Steffel et al, 2006; Wolfovitz, 2005). Multiple factors have been expression in endothelial cell (Mitchell et al, 2009; Steffel found to be involved in the regulation of TF synthesis and et al, 2005). Statins can competitively inhibit the rate-limiting enzyme of cholesterol synthesis when it indirectly inhibits the synthesis of intermediate products such as isoprenoid in the MVA pathway. These intermediate products are important mediators involved in the cellular signal transduction and complex intercellular communication
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