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Submitted on August 18, 2005
Accepted on January 4, 2006
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.
* To whom correspondence should be addressed. 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 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/
-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.
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