Intercellular Adhesion Molecule-1 Is Upregulated in Ischemic Muscle, Which Mediates Trafficking of Endothelial Progenitor Cells

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Abstract
Background— Trafficking of transplanted endothelial progenitor cells (EPCs) to an ischemic organ is a critical step in neovascularization. This study was performed to elucidate the molecular mechanism of EPC trafficking in terms of adhesion molecules. Methods and Results— Using murine hindlimb ischemia model, we examined expressions of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in ischemic muscle by immunofluorescence. ICAM-1 was overexpressed in ischemic muscle compared with nonischemic muscle, whereas expressions of E-selectin, VCAM-1, and PECAM-1 did not show that much difference. ICAM-1 was also upregulated by hypoxia in murine endothelial cells (ECs) as assessed by immunoblot and flow cytometry. EPCs were attached to ECs specifically through ICAM-1/β-2 integrin interaction in vitro. When EPCs were labeled with fluorescent dye or radioisotope (Tc-99m-HMPAO) and systemically administrate... This study was performed to elucidate the molecular mechanism of EPC homing. ICAM-1 expression in muscle is upregulated in response to ischemia. EPC attachment in vitro and EPC homing in vivo were significantly reduced by blocking ICAM-1. Our results suggest an important role of the ICAM-1 in EPCs homing to ischemic hindlimbs.