Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome.
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 40 mg/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 (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).


CONCLUSIONS
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.
Wei
Jia-li
JL
Department of Neurology, The Second Xiangya Hospital of Central South University, Hunan, PR China.
Cui
Hui-ming
HM
Ma
Chun-yang
CY
D000328:Adult; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000627:therapeutic use*; D013925:Thromboplastin / Q000187:drug effects* / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013925:Thromboplastin; D019821:Simvastatin