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

• Published in: European journal of medical research Vol. 12; no. 5; p. 216
• Main Authors: Wei, Jia-li, Cui, Hui-ming, Ma, Chun-yang
• Format: Journal Article
• Language: English
• Published: England 29.05.2007
• Subjects: Adult; Female; Gene Expression - drug effects; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - secretion; Male; Nephrotic Syndrome - drug therapy; Plasminogen Activator Inhibitor 1 - secretion; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Simvastatin - therapeutic use; Thromboplastin - drug effects; Thromboplastin - secretion
• ISSN: 0949-2321

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). 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 40 mg/day for 2 weeks. The activities of TF, PAI-1 and TF, PAI-1 mRNA of PBMCs were also measured. 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 (x10(3) AU/l) vs. 3.9 +/- 1.5(x10(3) AU/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 (x10(3) AU/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 (x10(3) AU/l) vs. 23.8 +/- 3.3 (x10(3) AU/l), P<0.05) secretion in PBMCs. 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). two-week 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). 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.