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


RESULTS
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.


CONCLUSIONS
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.
Kirmizis
Dimitrios
D
Department of Nephrology, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece. dkirmizis@bioprobe.gr
Papagianni
Aikaterini
A
Dogrammatzi
Fani
F
Skoura
Lemonia
L
Belechri
Anna-Maria
AM
Alexopoulos
Efstathios
E
Efstratiadis
Georgios
G
Memmos
Dimitrios
D
D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D008055:Lipids / Q000097:blood; D009000:Monocytes / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D006435:Renal Dialysis; D019821:Simvastatin / Q000494:pharmacology*
D015415:Biomarkers; D000960:Hypolipidemic Agents; D008055:Lipids; D002097:C-Reactive Protein; D019821:Simvastatin