Cytokine-Induced Mobilization of Circulating Endothelial Progenitor Cells Enhances Repair of Injured Arteries

TLDR

Circulating endothelial progenitor cells (CEPCs) are present in the bloodstream, can be mobilized by cytokines, and are recruited to injured vascular sites to aid repair. The study tests whether exogenous G‑CSF mobilizes CEPCs to accelerate arterial reendothelialization and reduce neointimal hyperplasia after injury. Male rats received daily G‑CSF or saline, underwent carotid balloon angioplasty, and were evaluated at 2 and 4 weeks post‑injury using flow cytometry, SEM, immunohistochemistry, and morphometric analysis. G‑CSF markedly increased circulating CEPCs, promoted >90% reendothelialization versus <20% in controls, reduced vascular inflammation, and cut neointimal thickness by about 60% at 2 and 4 weeks.

Abstract

The existence of circulating endothelial progenitor cells (CEPCs) has previously been documented. These cells can be mobilized by cytokines and are recruited to sites of injury, where they may participate in tissue repair. In the present study, we examined the hypothesis that mobilization of CEPCs by exogenous granulocyte-colony stimulating factor (G-CSF) enhances repair of injured arteries by facilitating reendothelialization and inhibiting neointima development.Male rats were injected daily with 50 microg/kg recombinant human G-CSF or 0.9% NaCl SC for 8 days. On the fifth day of treatment, 1 mL of blood was collected for fluorescence-activated cell sorting analysis of mononuclear cells, and the animals underwent balloon angioplasty of the common carotid artery. The animals were killed at 2 or 4 weeks after injury, and the carotid arteries were harvested and processed for immunohistochemistry, scanning electron microscopy (SEM), and morphometric analysis of endothelialization and neointimal formation. G-CSF increased the number of circulating mononuclear cells that express endothelial cell lineage markers several-fold. SEM and immunohistochemical staining with the endothelial marker, platelet and endothelial cell adhesion molecule-1, showed rapid and nearly complete (>90%) reendothelialization of the denuded vessels in the G-CSF-treated animals compared with <20% in the control animals. Reendothelialization was paralleled by a decrease in inflammation in the vessel wall. Neointima thickness was reduced by approximately 60% in the G-CSF-treated animals compared with control animals at 2 and 4 weeks after injury.We postulate that cytokine-induced mobilization of CEPCs may be a suitable therapeutic strategy for prevention of restenosis after revascularization procedures.