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Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome.
Eur J Med Res 2007; 12(5):216-21EJ

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 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).

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.

Authors+Show Affiliations

Department of Neurology, The Second Xiangya Hospital of Central South University, Hunan, PR China.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

17513194

Citation

Wei, Jia-li, et al. "Simvastatin Inhibits Tissue Factor and Plasminogen Activator Inhibitor-1 Secretion By Peripheral Blood Mononuclear Cells in Patients With Primary Nephrotic Syndrome." European Journal of Medical Research, vol. 12, no. 5, 2007, pp. 216-21.
Wei JL, Cui HM, Ma CY. Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome. Eur J Med Res. 2007;12(5):216-21.
Wei, J. L., Cui, H. M., & Ma, C. Y. (2007). Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome. European Journal of Medical Research, 12(5), pp. 216-21.
Wei JL, Cui HM, Ma CY. Simvastatin Inhibits Tissue Factor and Plasminogen Activator Inhibitor-1 Secretion By Peripheral Blood Mononuclear Cells in Patients With Primary Nephrotic Syndrome. Eur J Med Res. 2007 May 29;12(5):216-21. PubMed PMID: 17513194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome. AU - Wei,Jia-li, AU - Cui,Hui-ming, AU - Ma,Chun-yang, PY - 2007/5/22/pubmed PY - 2007/7/17/medline PY - 2007/5/22/entrez SP - 216 EP - 21 JF - European journal of medical research JO - Eur. J. Med. Res. VL - 12 IS - 5 N2 - 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). 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. SN - 0949-2321 UR - https://www.unboundmedicine.com/medline/citation/17513194/Simvastatin_inhibits_tissue_factor_and_plasminogen_activator_inhibitor_1_secretion_by_peripheral_blood_mononuclear_cells_in_patients_with_primary_nephrotic_syndrome_ L2 - https://medlineplus.gov/cholesterolmedicines.html DB - PRIME DP - Unbound Medicine ER -