Effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in patients on chronic hemodialysis

J Atheroscler Thromb. 2010 Dec 26;17(12):1256-65. doi: 10.5551/jat.5710. Epub 2010 Sep 25.

Abstract

Aim: We investigated the effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in hyperlipidemic endstage renal disease patients on chronic hemodialysis (HD).

Methods: In 25 hyperlipidemic HD patients who received 10 mg of simvastatin for 6 months and another 25 controls, the extended lipid profile and serum hsIL-6, MCP-1, sICAM-1, sVCAM-1, and sE-selectin, plasma oxLDL, and serum sFas and sFasL levels were determined at baseline, 3 months and 6 months. In 18 patients of the simvastatin group, the expression of CD14, CD16, CD62L and CD64 on monocyfes was determined with flow cytometry.

Result: Simvastatin treatment resulted in significant reductions in serum lipid levels at 3 months and beyond, compared to at baseline. Moreover, at 6 months, simvastatin caused a significant reduction in CRP (p < 0.001), which correlated to the decrease in total and LDL cholesterol levels, as well as a significant reduction in IL-6 (p=0.001), sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), oxLDL (p=0.001), sFas (p=0.02) and CD14 expression (p < 0.001), compared to baseline values. No significant changes in the controls were noticed during the study.

Conclusion: In conclusion, in hyperlipidemic HD patients, simvastatin treatment resulted in a significant reduction in markers of endothelial dysfunction, inflammation, oxidative stress, endothelial cell apoptosis and peripheral blood monocyte stimulation. The reduction in CRP appears to be related to the lipid-lowering effects of simvastatin.

MeSH terms

  • Apoptosis / drug effects
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Endothelial Cells / drug effects
  • Humans
  • Hypolipidemic Agents / pharmacology
  • Inflammation / drug therapy
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / therapy
  • Lipids / blood
  • Monocytes / drug effects
  • Oxidative Stress / drug effects
  • Renal Dialysis
  • Simvastatin / pharmacology*

Substances

  • Biomarkers
  • Hypolipidemic Agents
  • Lipids
  • C-Reactive Protein
  • Simvastatin