Propranolol inhibits endothelial progenitor cell homing: a possible treatment mechanism of infantile hemangioma

Abstract

Propranolol effectively treats infantile hemangioma, but its mechanisms of action remain poorly understood. Although the antiangiogenesis role of propranolol has been previously demonstrated, several lines of evidence suggest that this therapeutic agent may affect the neovascular formation in infantile hemangioma by targeting vasculogenesis. In addition, the homing of endothelial progenitor cells to the lesion of infantile hemangioma plays an important role during the process of vasculogenesis. The purpose of this study was to investigate whether propranolol inhibits the vasculogenesis in infantile hemangioma by targeting endothelial progenitor cells recruitment. Endothelial progenitor cells were treated with different concentrations (0, 1, 5, 10, 20, 40, 60, 80, 100 μM) of propranolol for indicated times (24, 48, 72 h). Cell proliferation and viability were assessed by MTT assay and trypan blue staining. Cell migration was determined by wound healing assay and Boyden chamber assay. The expression levels of extracellular signal regulated kinase, phospho-extracellular signal regulated kinase, Akt, and phospho-Akt were measured by Western blot analysis to explore the molecular mechanism of propranolol on endothelial progenitor cells. In addition, the expression of CXCR4 was measured by Western blot and reverse transcriptase polymerase chain reaction. Propranolol did not significantly affect the proliferation of endothelial progenitor cells. It inhibited stromal-cell-derived factor 1α-induced migration of endothelial progenitor cells through the Akt and MAPK pathways and the expression of CXCR4 in a dose- and time-dependent manner. In addition, the expression of CXCR4 was suppressed by propranolol most likely through the Akt and MAPK pathways. Propranolol inhibits stromal-cell-derived factor 1α-induced endothelial progenitor cell homing by suppressing the expression of CXCR4 most likely through the Akt and MAPK pathways.