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

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)1066-1072
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Adhesion molecules
  • Angiogenesis
  • Endothelial progenitor cells
  • Endothelium
  • Ischemia

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