Arteriogenesis proceeds via ICAM-1/Mac-1-mediated mechanisms

Imo E. Hoefer, Niels Van Royen, John E. Rectenwald, Elisabeth Deindl, Jing Hua, Marco Jost, Sebastian Grundmann, Michiel Voskuil, C. Keith Ozaki, Jan J. Piek, Ivo R. Buschmann

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Monocyte adhesion to shear stress-activated endothelium stands as an important initial step during arteriogenesis (collateral artery growth). Using multiple approaches, we tested the hypothesis that monocyte adhesion via intercellular adhesion molecule-1 (ICAM-1) and selectin interactions is essential for adaptive arteriogenesis. Forty-eight New Zealand White rabbits received either solvent, monocyte chemoattractant protein-1 (MCP-1) alone, MCP-1 plus ICAM-mab, or MCP-1 plus an IgG2a isotype control via osmotic minipumps. After 7 days, collateral conductance was evaluated: solvent 4.01 (mL/min per 100 mm Hg), MCP-1 plus ICAM-mab 8.04 (versus solvent P=NS), and MCP-1 alone 33.11 (versus solvent P<0.05). Furthermore, the right femoral arteries of ICAM-1-/-, Mac-1-/- and mice having defective selectin interactions (FT4/7-/-) as well as their corresponding controls were ligated. One week later, perfusion ratios were determined by the use of fluorescent microspheres. FT4/7-/- mice did not show any significant difference in perfusion restoration whereas ICAM-1-/- and Mac-1-/- mice had a significant reduction in arteriogenesis as compared with matching controls (FT4/7-WT 37±9%, FT4/7-/- 32±3%, P=0.31; C57BL/6J 59±9%, ICAM-1-/- 36±8%, P<0.05; Mac-1-/- 42±3%, P<0.05). ICAM-1/Mac-1-mediated monocyte adhesion to the endothelium of collateral arteries is an essential step for arteriogenesis, whereas this process can proceed via selectin interaction independent mechanisms. Furthermore, in vivo treatment with monoclonal antibodies against ICAM-1 totally abolishes the stimulatory effect of MCP-1 on collateral artery growth, suggesting that the mechanism of the MCP-1-induced arteriogenesis proceeds via the localization of monocytes rather than the action of the MCP-1 molecule itself.

Original languageEnglish (US)
Pages (from-to)1179-1185
Number of pages7
JournalCirculation research
Issue number9
StatePublished - May 14 2004


  • Blood flow
  • Cell adhesion molecules
  • Collateral circulation
  • Intercellular adhesion molecule-1
  • Microspheres

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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