Published online before print July 6, 2006, doi: 10.1161/01.RES.0000235986.35957.a3
© 2006 American Heart Association, Inc.
Integrative Physiology |
Essential Role of ICAM-1/CD18 in Mediating EPC Recruitment, Angiogenesis, and Repair to the Infarcted Myocardium
From the Department of Medicine (Y.W., J.H., L.Z., K.M., R.E.P., V.J.D.), Duke University School of Medicine, Durham, NC; and Department of Medicine (Y.W., J.E.I., L.Z., K.M., C.-C.L., R.E.P., V.J.D.), Brigham & Women’s Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Victor J. Dzau, MD, Duke University Medical Center & Health System, DUMC 3701, Durham, NC 27710. E-mail victor.dzau{at}duke.edu
Bone marrow–derived endothelial progenitor cells (EPCs) have the ability to migrate to ischemic organs. However, the signals that mediate trafficking and recruitment of these cells are not well understood. Using a functional genomics strategy, we determined the genes that were upregulated in the ischemic myocardium and might be involved in EPC recruitment. Among them, CD18 and its ligand ICAM-1 are particularly intriguing because CD18 and its heterodimer binding chains CD11a and CD11b were correspondingly expressed in ex vivo–expanded EPCs isolated from rat and murine bone marrows. To further verify the functional role of CD18 in mediating EPC recruitment and repair to the infarcted myocardium, we used neutralizing antibody to block CD18. Blockade of CD18 in EPCs significantly inhibited their attachment capacity in vitro and reduced their recruitment to the ischemic myocardium in vivo by 95%. Moreover, mice receiving EPCs that were treated with control isotype IgG exhibited significantly increased capillary density in the infarct border zone, reduced cardiac dilatation, ventricular wall thinning, and fibrosis when compared with myocardial infarction mice receiving PBS and CD18 blockade reversed the EPC-mediated improvements to the infarcted heart. Thus, our results suggest an essential role of CD18 in mediating EPC recruitment and the subsequent functional effects on the infarcted heart.
Key Words: CD18 • EPC • recruitment • myocardial infarction • heart repair
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