SDF-1alpha involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice

Abstract

Background: Endothelial progenitor cells (EPCs) can be mobilized by cytokines and recruited to sites of neovascularization and neointima, where they differentiate into mature endothelial cells. It is thought that stromal cell-derived factor-1alpha (SDF-1alpha) is involved in ischemia-mediated mobilization and homing of EPCs and in vascular injury-mediated mobilization and homing of vascular smooth muscle progenitor cells. It is unclear if SDF-1alpha plays a similar role in the mobilization and recruitment of EPCs after vascular injury.

Methods and results: SDF-1alpha was detected by reverse transcriptase-polymerase chain reaction and Western blot in the carotid arteries of mice at different times after wire-induced injury. SDF-1alpha expression was evident at 1 day and peaked at 3 days after arterial injury. In an ELISA test, a rise in the plasmatic concentration of SDF-1alpha and a significant reduction of SDF-1alpha bone marrow (BM) concentration were noticed at different times after injury (Days 1, 3, and 7). Fluorescence-activated cell sorting analysis revealed that the amount of circulating EPCs was increased shortly after induction of vascular injury and persisted for up to 7 days. In SDF-1alpha antibody-treated mice, only a small rise in the amount of circulating EPCs was noted at 1 day. En-face microscopy and immunohistochemical analysis showed that systemic injection of EPCs after vascular injury demonstrated their recruitment to the sites of endothelial denudation, where they could adopt an endothelium-like phenotype and accelerate reendothelialization of the injured arteries. Fewer CXCR4 (receptor of SDF-1)-blocked EPCs could home to the sites of endothelial denudation, and accelerated reendothelialization was not observed in this group. Treatment of mice after carotid injury with a neutralizing SDF-1alpha monoclonal antibody for 2 weeks reduced reendothelialization area.

Conclusion: We demonstrated for the first time that SDF-1alpha plays an important role in reendothelialization after vascular injury in mice. This contribution appears to be attributable to SDF-1alpha-dependent mobilization and recruitment of circulating EPCs.