Regulation of endothelial progenitor cell homing after arterial injury

Mihail Hristov; Alma Zernecke; Elisa A. Liehn; Christian Weber

doi:10.1160/TH07-03-0181

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(02): 274-277
DOI: 10.1160/TH07-03-0181

Theme Issue Article

Schattauer GmbH

Regulation of endothelial progenitor cell homing after arterial injury

Mihail Hristov

¹Institute for Molecular Cardiovascular Research (IMCAR)

²Interdisciplinary Center for Clinical Research “BIOMAT”, University Hospital Aachen, Aachen, Germany

,

Alma Zernecke

¹Institute for Molecular Cardiovascular Research (IMCAR)

,

Elisa A. Liehn

¹Institute for Molecular Cardiovascular Research (IMCAR)

²Interdisciplinary Center for Clinical Research “BIOMAT”, University Hospital Aachen, Aachen, Germany

,

Christian Weber

¹Institute for Molecular Cardiovascular Research (IMCAR)

²Interdisciplinary Center for Clinical Research “BIOMAT”, University Hospital Aachen, Aachen, Germany

› Author Affiliations

Abstract

Summary

Adult bone marrow and peripheral blood contain sub-populations of vascular precursor cells, which can differentiate into mature endothelial cells and have therefore been commonly termed endothelial progenitor cells (EPCs). Although EPCs encompass rather heterogeneous cell sub-populations of multiple origins and localization, these cells were basically characterized by expression of progenitor markers and by the development of colony-forming units and late endothelial outgrowth with terminal differentiation into mature endothelial cells. Notably, functional studies in vivo have implied the contribution of EPCs to therapeutic reendothelialization and inhibition of neointimal growth following endothelial injury. In the context of this regenerative arterial remodeling, an adequate homing of EPCs plays a central role. This multi-step process of EPC mobilization, recruitment and firm adhesion is regulated by key angiogenic chemokines (CCL2, CXCL1, CXCL7, CXCL12) and their respective receptors (CCR2, CXCR2, CXCR4). Furthermore, the recruitment of circulating EPCs to sites of arterial injury is synchronized by activated platelets and adhesion molecules of the selectin and integrin family. Thus, translating this molecular knowledge to interventional cardiovascular medicine,such a detailed understanding in the complex regulation of EPC homing may be helpful for more effectively preventing “in-stent” stenosis by facilitating stent endothelialization.

Keywords

Adhesion molecules - atherosclerosis - endothelial cells

Full Text

References

References
1 Cines DB. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-3561.
2 Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med 2004; 8: 498-508.
3 Rabelink TJ. et al. Endothelial progenitor cells: more than an inflammatory response?. Arterioscler Thromb Vasc Biol 2004; 24: 834-838.
4 Asahara T. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-967.
5 Peichev M. et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000; 95: 952-958.
6 Werner N. et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res 2003; 93: e17-24.
7 Kalka C. et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000; 97: 3422-3427.
8 Ceradini DJ. et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 2004; 10: 858-864.
9 Romagnani P. et al. CD14⁺CD34^low cells with stem cell phenotypic and functional features are themajor source of circulating endothelial progenitors. Circ Res 2005; 97: 314-322.
10 Elsheikh E. et al. Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity. Blood 2005; 106: 2347-2355.
11 Rehman J. et al. Peripheral blood “endothelial progenitor cells“ are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 2003; 107: 1164-1169.
12 Gulati R. et al. Diverse origin and function of cells with endothelial phenotype obtained from adult human blood. Circ Res 2003; 93: 1023-1025.
13 Weber C. et al. Chemokines: key regulators of mononuclear cell recruitment in atherosclerotic vascular disease. Arterioscler Thromb Vasc Biol 2004; 24: 1997-2008.
14 Schober A, Zernecke A. Chemokines in vascular remodeling. Thromb Haemost 2007; 97: 730-737.
15 Chavakis E. et al. Role of β2-integrins for homing and neovascularization capacity of endothelial progenitorcells. J Exp Med 2005; 201: 63-72.
16 Duan H. et al. LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue. Thromb Haemost 2006; 96: 807-815.
17 Blindt R. et al. A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells. J Am Coll Cardiol 2006; 47: 1786-1795.
18 De Boer HC. et al. Fibrin and activated plateletsco operatively guide stem cells to a vascular injury and promote differentiation towards an endothelial cell phenotype. Arterioscler Thromb Vasc Biol 2006; 26: 1653-1659.
19 Zernecke A. et al. SDF-1α/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscleprogenitor cells. Circ Res 2005; 96: 784-791.
20 Hristov M. et al. Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res 2007; 100: 590-597.
21 Urbich C. et al. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 2005; 39: 733-742.
22 Wysocki SJ. et al. Monocyte chemoattractant protein-1 gene expression in injured pig artery coincides with early appearance of infiltrating monocyte/macrophages. J Cell Biochem 1996; 62: 303-313.
23 Goede V. et al. Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer 1999; 82: 765-770.
24 Buschmann I. et al. Influence of inflammatory cytokines on arteriogenesis. Microcirculation 2003; 10: 371-379.
25 Weber KS. et al. Expression of CCR2 by endothelial cells: implications for MCP-1 mediated wound injury repair and In vivo inflammatory activation of endothelium. Arterioscler Thromb Vasc Biol 1999; 19: 2085-2093.
26 Spring H. et al. Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci USA 2005; 102: 18111-18116.
27 Fujiyama S. et al. Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells. Circ Res 2003; 93: 980-989.
28 Zernecke A. et al. Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10. Blood 2006; 107: 4240-4243.
29 Schober A. et al. SDF-1α-mediated tissue repair by stem cells: a promising tool in cardiovascular medicine?. Trends Cardiovasc Med 2006; 16: 103-108.
30 Massberg S. et al. Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med 2006; 203: 1221-1233.
31 Guleng B. et al. Blockade of the SDF-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner. Cancer Res 2005; 65: 5864-5871.
32 Walter DH. et al. Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res 2005; 97: 1142-1151.
33 Smith ML. et al. CXCR2–and E-selectin-induced neutrophil arrest during inflammation in vivo. J Exp Med 2004; 200: 935-939.
34 Zernecke A. et al. Combinatorial model of chemokine involvement in glomerular monocyte recruitment: role of CXC chemokine receptor 2 in infiltration during nephrotoxic nephritis. J Immunol 2001; 166: 5755-5762.
35 Huo Y. et al. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium. J Clin Invest 2001; 108: 1307-1314.
36 Liehn EA. et al. Blockade of keratinocyte-derived chemokine inhibits endothelial recovery and enhances plaque formation after arterial injury in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2004; 24: 1891-1896.
37 Haghnegahdar H. et al. The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma. J Leukoc Biol 2000; 67: 53-62.
38 Smith C. et al. Increased levels of neutrophil-activating peptide-2 in acute coronary syndromes: possible role of platelet-mediated vascular inflammation. J Am Coll Cardiol 2006; 48: 1591-1599.
39 Vajkoczy P. et al. Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med 2003; 197: 1755-1765.
40 Foubert P. et al. PSGL-1-mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells. J Clin Invest 2007; 117: 1527-1537.
41 Laudanna C, Alon R. Right on the spot. Chemokine triggering of integrin-mediated arrest of rolling leukocytes. Thromb Haemost 2006; 95: 5-11.
42 Weber KS. et al. Specific activation of leukocyte beta2 integrins lymphocyte function-associated antigen-1 and Mac-1 by chemokines mediated by distinct pathways via the alpha subunit cytoplasmic domains. Mol Biol Cell 1999; 10: 861-873.
43 Weber C. et al. Enhancement of monocyte adhesion to endothelial cells by oxidatively modified low-density lipoprotein is mediated by activation of CD11b. Biochem Biophys Res Commun 1995; 206: 621-628.
44 Jin H. et al. A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature. J Clin Invest 2006; 116: 652-662.
45 Walter DH. et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 2002; 105: 3017-3024.
46 Walter DH. et al. Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis. Circulation 2004; 110: 36-45.
47 Lucerna M. et al. Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment. Blood 2007; 109: 122-129.
48 Aoki J. et al. Endothelial progenitor cell capture by stents coated with antibody against CD34:the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J Am Coll Cardiol 2005; 45: 1574-1579.
49 Rotmans JI. et al. In vivo cell seeding with anti-CD34 antibodies successfully accelerates endothelialization but stimulates intimal hyperplasia in porcine arteriovenous expanded polytetrafluoroethylene grafts. Circulation 2005; 112: 12-18.
50 Weber C. Platelets and chemokines in atherosclerosis: partners in crime. Circ Res 2005; 96: 612-616.
51 Langer H. et al. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro. Circ Res 2006; 98: e2-10.