This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 99/3/315    most recent 01.RES.0000235986.35957.a3v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, Y. Articles by Dzau, V. J. Search for Related Content PubMed PubMed Citation Articles by Wu, Y. Articles by Dzau, V. J. Related Collections Other myocardial biology Endothelium/vascular type/nitric oxide Angiogenesis Animal models of human disease Physiological and pathological control of gene expression

(Circulation Research. 2006;99:315.)
© 2006 American Heart Association, Inc.

Integrative Physiology

Essential Role of ICAM-1/CD18 in Mediating EPC Recruitment, Angiogenesis, and Repair to the Infarcted Myocardium

Yaojiong Wu, James E. Ip, Jing Huang, Lunan Zhang, Kenichi Matsushita, Choong-Chin Liew, Richard E. Pratt, Victor J. Dzau

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

This article has been cited by other articles:

				M. R. Schroeter, M. Leifheit, P. Sudholt, N.-M. Heida, C. Dellas, I. Rohm, F. Alves, M. Zientkowska, S. Rafail, M. Puls, et al. Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion Circ. Res., August 29, 2008; 103(5): 536 - 544. [Abstract] [Full Text] [PDF]

				M. S. Penn and A. A. Mangi Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy Circ. Res., June 20, 2008; 102(12): 1471 - 1482. [Abstract] [Full Text] [PDF]

				E. Chavakis, G. Carmona, C. Urbich, S. Gottig, R. Henschler, J. M. Penninger, A. M. Zeiher, T. Chavakis, and S. Dimmeler Phosphatidylinositol-3-Kinase-{gamma} Is Integral to Homing Functions of Progenitor Cells Circ. Res., April 25, 2008; 102(8): 942 - 949. [Abstract] [Full Text] [PDF]

				G. Marsboom, P. Pokreisz, O. Gheysens, P. Vermeersch, H. Gillijns, M. Pellens, X. Liu, D. Collen, and S. Janssens Sustained Endothelial Progenitor Cell Dysfunction After Chronic Hypoxia-Induced Pulmonary Hypertension Stem Cells, April 1, 2008; 26(4): 1017 - 1026. [Abstract] [Full Text] [PDF]

				G. Carmona, E. Chavakis, U. Koehl, A. M. Zeiher, and S. Dimmeler Activation of Epac stimulates integrin-dependent homing of progenitor cells Blood, March 1, 2008; 111(5): 2640 - 2646. [Abstract] [Full Text] [PDF]

				Y. Wu, L. Chen, P. G. Scott, and E. E. Tredget Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis Stem Cells, October 1, 2007; 25(10): 2648 - 2659. [Abstract] [Full Text] [PDF]

				J. Hur, C.-H. Yoon, C.-S. Lee, T.-Y. Kim, I.-y. Oh, K.-W. Park, J.-H. Kim, H.-S. Lee, H.-J. Kang, I.-H. Chae, et al. Akt Is a Key Modulator of Endothelial Progenitor Cell Trafficking in Ischemic Muscle Stem Cells, July 1, 2007; 25(7): 1769 - 1778. [Abstract] [Full Text] [PDF]