[PDF][PDF] Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic …

J Wei, H Cui, C Ma - European journal of medical research, 2007 - daignet.de
J Wei, H Cui, C Ma
European journal of medical research, 2007daignet.de
Background: Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or
expression are upregulated in nephrotic syndrome. Despite extensive research on
antithrombotic effect of statins, little is known about their effects on TF and PAI-1 expression
in peripheral blood mononuclear cells in patients with primary nephrotic syndrome (PNS).
Methods: PBMCs were isolated by gradient centrifugation from 25 individuals with PNS and
25 healthy subjects. TF and PAI-1 mRNA were detected by RT-PCR. The activities of TF and …
Abstract
Background: Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in nephrotic syndrome. Despite extensive research on antithrombotic effect of statins, little is known about their effects on TF and PAI-1 expression in peripheral blood mononuclear cells in patients with primary nephrotic syndrome (PNS). Methods: PBMCs were isolated by gradient centrifugation from 25 individuals with PNS and 25 healthy subjects. TF and PAI-1 mRNA were detected by RT-PCR. The activities of TF and PAI-1 were determined with ELISA and chromogenic substrate method, respectively. The patients with PNS were then treated with simvastatin 40mg/day for 2 weeks. The activities of TF, PAI-1 and TF, PAI-1 mRNA of PBMCs were also measured.
Results: Compared with controls, patients with PNS had increased TF, PAI-1 secretion by PBMCs at baseline [70.4±15.6 ng/l vs. 32.7±8.2 ng/l; 15.9±2.4 (χ103AU/l) vs. 3.9±1.5 (χ103AU/l), P< 0.01] and after stimulated by LPS (10 ng/mL)[89.2±13.4 ng/l vs. 49.5±10.3 ng/l; 23.8±3.3 (χ103AU/l) vs. 8.1±2.1, P< 0.01]. The simvastatin treatment resulted in a significant effect in decreasing TF and PAI-1 [69.1±14.6 ng/l vs. 89.2±13.4 ng/l; 16.5±4.8 (χ103AU/l) vs. 23.8±3.3 (χ103AU/l), P< 0.05] secretion in PBM-Cs. Increased TF and PAI-1 mRNA expression in PBMCs from PNS (1.034±0.043 and 0.982±0.056, respectively) as compared to the control (0.221±0.015 and 0.221±0.015, respectively)(p< 0.01). twoweek simvastatin treatment resulted in significant decrease of TF (0.535±0.028, p< 0.01) and PAI-1 mRNA (0.602±0.037, p< 0.01). Conclusion: TF and PAI-1 mRNA expression and activities in PBMCs were increased in PNS. Simvastatin reduced TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of statins in the treatment of PNS.
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