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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1066.)
© 2006 American Heart Association, Inc.

Vascular Biology

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

Chang-Hwan Yoon; Jin Hur; Il-Young Oh; Kyung-Woo Park; Tae-Youn Kim; Jae-Hoon Shin; Ji-Hyun Kim; Choon-Soo Lee; June-Key Chung; Young-Bae Park; Hyo-Soo Kim

From the Cardiovascular Laboratory (C.-H.Y., J.H., I.O., K.-W.P., T.-Y.K., J.-H.K., C.-S.L., Y.-B.P., H.-S.K.), Clinical Research Institute, Seoul National University Hospital; Department of Nuclear Medicine (J.-H.S., J.-K.C.), Seoul National University College of Medicine; Department of Internal Medicine (Y.-B.P., H.-S.K.), Seoul National University College of Medicine, Seoul, Korea.

Correspondence to Hyo-Soo Kim, MD or Young-Bae Park, MD, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea. E-mail hyosoo{at}snu.ac.kr

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/ß-2 integrin interaction in vitro. When EPCs were labeled with fluorescent dye or radioisotope (Tc-99m-HMPAO) and systemically administrated in vivo, EPCs preferentially homed to ischemic muscle. By blocking ICAM-1, EPCs entrapment to ischemic limb in vivo was significantly reduced and neovascularization induced by EPC transplantation was attenuated.

Conclusions— ICAM-1 is upregulated by ischemia, and this is closely associated with EPCs entrapment to ischemic limb. Our findings suggest that ICAM-1 expression might be important in regulating the process of neovascularization through its ability to recruit EPCs.

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.

Key Words: angiogenesis • adhesion molecules • endothelium • endothelial progenitor cells • ischemia

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