Simvastatin and rosuvastatin mobilize Endothelial Progenitor Cells but do not prevent their acute decrease during systemic inflammation

Abstract

Introduction: 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.

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

Materials and 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.