Simvastatin and rosuvastatin mobilize Endothelial Progenitor Cells but do not prevent their acute decrease during systemic inflammation.
BACKGROUND
Endothelial Progenitor Cells (EPCs) are a specific subtype of haematopoietic stem cells that contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC counts in patients with stable coronary artery disease. Numbers of circulating EPCs decrease in various inflammatory diseases. Thus, we hypothesized that short term statin pre-treatment may alter the acute change in EPC levels during systemic inflammation.


OBJECTIVE
To explore the effect of statin pretreatment and low grade experimental endotoxemia on endothelial progenitor cells in humans.


METHODS
Randomized, double-blind, placebo-controlled three way cross-over trial in six healthy male volunteers. Each volunteer received three treatments consisting of 5 days of oral simvastatin (80 mg/day), rosuvastatin (40 mg/day) or placebo. On Day 5 of each study period, subjects received lipopolysaccharide (LPS; 2 ng/kg i.v.). This trial has been registered with Clinical.Trials.gov, trial number NCT00309374.


RESULTS
Statin pre-treatment led to a significant increase in circulating EPCs (1.9-3.5 fold, depending on statin and analytic method; P<0.05) but could not suppress the endotoxemia induced EPC decrease (approximately -75%; P<0.05) during the observation period.


CONCLUSIONS
Statin therapy significantly increases EPCs within 96 hours and this may be a class effect. However, statins could not counteract the acute decrease in circulating EPCs after LPS infusion.
Spiel
Alexander O
AO
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Mayr
Florian B
FB
Leitner
Judith M
JM
Firbas
Christa
C
Sieghart
Wolfgang
W
Jilma
Bernd
B
D000328:Adult; D002452:Cell Count; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D011743:Pyrimidines; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D000068718:Rosuvastatin Calcium; D019821:Simvastatin