Repair of Lipopolysaccharide-Induced Acute Lung Injury in Mice by Endothelial Progenitor Cells, Alone and in Combination With Simvastatin

Abstract

Endothelial progenitor cells (EPCs) are involved in endothelium repair of acute lung injury (ALI). Numerous studies have demonstrated that statins can promote EPC function in vitro and in vivo; therefore, the purpose of this study was to determine whether simvastatin enhances the function of EPCs participating in the repair of ALI. BALB/C mice were initially pretreated with simvastatin by intraperitoneal administration 24 h before, and again at the time of, intratracheal instillation of lipopolysaccharide (LPS) and subsequently treated with EPCs by i.v. transplantation 2 h later. The effects of capillary permeability, endothelium repair, and inflammatory cytokines were measured. This study revealed that both simvastatin administration and EPC transplantation can reduce the severity of LPS-induced ALI in mice, and the effect can be further improved by combining the two therapies. The administration of simvastatin and EPC transplantation can reduce the severity of LPS-induced ALI in mice, and improvement is moderately enhanced in some respects when EPC transplantation is combined with simvastatin administration. The beneficial role of simvastatin on EPCs may be a component of its pleiotropic effects. Although the exact mechanism remains unknown, the combined administration of simvastatin and EPC transplantation may be a potentially important, cell-based, inflammation-mediated therapy for patients with ALI/ARDS.