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Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 expression of glomerular mesangial cells in

Jiali Wei1, Chunyang Ma, Xiaomeng Wang

  • 1Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.

Biomedical Research (Tokyo, Japan)
|September 15, 2006
PubMed

Insights

Simvastatin reduces kidney tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) in hypercholesterolemia. This suggests simvastatin may protect against kidney microthrombus formation and obesity-related glomerulopathy.

Area of Science:

  • Nephrology
  • Cardiovascular Research
  • Pharmacology

Background:

  • Hypercholesterolemia elevates tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1).
  • The impact of statins on TF and PAI-1 in glomerular mesangial cells during hypercholesterolemia is not well understood.
  • Glomerular mesangial cells play a role in kidney function and disease.

Purpose of the Study:

  • To investigate the effect of simvastatin on TF and PAI-1 expression in glomerular mesangial cells of hypercholesterolemic rabbits.
  • To determine if simvastatin can mitigate hypercholesterolemia-induced pro-thrombotic changes in the kidney.

Main Methods:

  • Rabbits were fed a high-cholesterol diet for 8 weeks, followed by simvastatin or starch treatment for 4 weeks.
  • TF and PAI-1 mRNA levels in glomerular mesangial cells were quantified using RT-PCR.
  • Plasma TF and PAI-1 activities were measured using ELISA and chromogenic assays.

Main Results:

  • High-cholesterol diet significantly increased serum total cholesterol and triglyceride levels.
  • Hypercholesterolemia led to increased TF and PAI-1 mRNA in mesangial cells and plasma.
  • Simvastatin treatment significantly reduced mesangial TF and PAI-1 mRNA and plasma TF and PAI-1 activities.

Conclusions:

  • Simvastatin effectively downregulates TF and PAI-1 expression and activity in hypercholesterolemic rabbits.
  • Simvastatin may offer kidney protection against microthrombus formation in hypercholesterolemic states.
  • These findings suggest a potential role for simvastatin in managing obesity-related glomerulopathy.

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