EFFECTS OF SHORT TERM STATIN PRE-TREATMENT AND SUBSEQUENT LOW DOSE ENDOTOXEMIA ON CIRCULATING ENDOTHELIAL PROGENITOR CELLS IN HEALTHY VOLUNTEERS
Abstract number: P-M-365
Spiel1 A.O., Mayr1 F.B., Leitner1 J.M., Firbas1 C., Sieghart1 W., Jilma1 B.
1Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
How-to-cite Spiel AO, Mayr FB, Leitner JM, Firbas C, Sieghart W, Jilma B. EFFECTS OF SHORT TERM STATIN PRE-TREATMENT AND SUBSEQUENT LOW DOSE ENDOTOXEMIA ON CIRCULATING ENDOTHELIAL PROGENITOR CELLS IN HEALTHY VOLUNTEERS. J Thromb Haemost 2007; 5 Supplement 2: P-M-365
Introduction: Endothelial Progenitor Cells (EPCs) are a subtype of haematopoietic stem cells mobilized from the bone marrow into the circulation. EPCs have been investigated with partly inconsistent results in different inflammatory disease states.
Statins exert pleiotropic beneficial effects. For example, statins have been shown to increase peripheral EPCs via stimulation of the PI 3-kinase/Akt signaling pathway in patients with stable coronary artery disease (CAD).
Since data on EPCs in systemic inflammation are scarce, we used the human endotoxemia model to quantify the effects of short term statin pre-treatment and subsequent LPS challenge on the changes in circulating EPC levels. This model has been shown to be sensitive to the anti-inflammatory properties of statins.
Methods: Randomized, double-blind, placebo-controlled three way cross-over trial in six healthy male volunteers with a washout-time between treatment periods of at least 6 weeks. Each volunteer received 5 days of oral Simvastatin (80mg/day), Rosuvastatin (40mg/day) and placebo pre-treatment. On Day 5 of each study period, subjects received LPS (2 ng/kg i.v.) and EPC counts were determined at time points 0, 2, 4, 6 and 24 hours.
Results: Pre-treatment with simvastatin increased EPCs 2.1 fold (FACS analysis) and 3.5 fold (CFU assay), and Rosuvastatin (40mg/d) increased EPCs 1.9 fold (FACS analysis) and 2.6 fold (CFU assay) compared to baseline. Placebo treatment did not affect EPC counts.
LPS challenge decreased EPC counts about 76%, with nadir levels after 4 to 6 hours and no significant difference in nadir levels between treatments. Circulating EPCs returned to values comparable to those before LPS-challenge 24 hours thereafter.
Statin pretreatment increased baseline EPC values but did not suppress the endotoxemia induced EPC decrease over the observation period.
Conclusions: Short term statin therapy significantly increases EPCs in healthy volunteers, but could not not suppress the endotoxemia induced EPC decrease over the observation period.