Download PDF
Hamostaseologie 2016; 36(02): 97-102
DOI: 10.5482/HAMO-14-10-0054
Review
Schattauer GmbH

Potential cell-specific functions of CXCR4 in atherosclerosis

Potenziell zellspezifische Funktionen des Rezeptors CXCR4 in der Atheroklerose
Christian Weber
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
3   Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands
,
Yvonne Döring
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
,
Heidi Noels
4   Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
› Author Affiliations
Further Information

Publication History

received: 19 October 2014

accepted in revised form: 27 January 2014

Publication Date:
20 December 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Der Chemokinrezeptor CXCR4 and sein Ligand CXCL12 bilden eine wichtige Achse in der Regulation von Zellfunktionen bei normaler Homöostase und bei Erkrankungen. Zusätzlich kann der atypische CXCL12 Rezeptor CXCR7 die Verfügbarkeit und Funktion von CXCL12 modulieren. Neben ihrer Rolle in der Mobilisierung von Stamm- und Vorläuferzellen, können CXCR4 und CXCL12 auch die Entwicklung der Atherosklerose über verschiedene Zellfunktionen beeinflussen. Dieser kurze Übersichtsartikel fasst das gegenwärtige Wissen zu den zellspezifischen Funktionen von CXCL12 und den Rezeptoren CXCR4 und CXCR7 mit möglichen Implikationen für die Entstehung und Progression der Atherosklerose zusammen

Summary

The chemokine CXCL12 and its receptor CXCR4 form an important axis contributing to cellular functions in homeostasis and disease. In addition, the atypical CXCL12 receptor CXCR7 may shape the availability and function of CXCL12. Further to their role through progenitor cell mobilization, CXCL12 and CXCR4 may affect native atherogenesis by modifying atherosclerosis-relevant cellular functions.

This short review intends to provide a concise summary of current knowledge with regards to cell-specific functions of CXCL12 and its receptors CXCR4 and CXCR7 with potential implications for the initiation and progression of atherosclerosis.

Schlüsselwörter

CXCL12 - CXCR4 - CXCR7

Keywords

CXCL12 - CXCR4 - CXCR7
 

  • References

  • 1 Zernecke A, Weber C. Chemokines in atherosclerosis: proceedings resumed. Arterioscler Thromb Vasc Biol 2014; 34: 742-750.
    CrossrefPubMedGoogle Scholar
  • 2 Bruhl H, Cohen CD, Linder S. et al. Post-translational and cell type-specific regulation of CXCR4 expression by cytokines. Eur J Immunol 2003; 33: 3028-3037.
    CrossrefPubMedGoogle Scholar
  • 3 Murphy PM, Baggiolini M, Charo IF. et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 2000; 52: 145-176.
    PubMedGoogle Scholar
  • 4 Nie Y, Waite J, Brewer F. et al. The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J Exp Med 2004; 200: 1145-1156.
    CrossrefPubMedGoogle Scholar
  • 5 Gupta SK, Lysko PG, Pillarisetti K. et al. Chemokine receptors in human endothelial cells. J Biol Chem 1998; 273: 4282-4287.
    CrossrefPubMedGoogle Scholar
  • 6 Nemenoff RA, Simpson PA, Furgeson SB. et al. Targeted deletion of PTEN in smooth muscle cells results in vascular remodeling and recruitment of progenitor cells through induction of stromal cell-derived factor-1alpha. Circ Res 2008; 102: 1036-1045.
    CrossrefPubMedGoogle Scholar
  • 7 Jie W, Wang X, Zhang Y. et al. SDF-1alpha/CXCR4 axis is involved in glucose-potentiated proliferation and chemotaxis in rat vascular smooth muscle cells. Int J Exp Pathol 2010; 91: 436-444.
    CrossrefPubMedGoogle Scholar
  • 8 Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 2011; 17: 1410-1422.
    CrossrefPubMedGoogle Scholar
  • 9 Tanaka G, Nakase I, Fukuda Y. et al. CXCR4 stimulates macropinocytosis. Chem Biol 2012; 19: 1437-1446.
    CrossrefPubMedGoogle Scholar
  • 10 Ma W, Liu Y, Ellison N, Shen J. Induction of C-X-C chemokine receptor type 7 switches stromal cell-derived factor-1 signaling and phagocytic activity in macrophages linked to atherosclerosis. J Biol Chem 2013; 288: 15481-15494.
    CrossrefPubMedGoogle Scholar
  • 11 Li X, Zhu M, Penfold ME. et al. Activation of CXCR7 limits atherosclerosis and improves hyper-lipidemia by increasing cholesterol uptake in adi-pose tissue. Circulation 2014; 129: 1244-1253.
    CrossrefPubMedGoogle Scholar
  • 12 Ingersoll MA, Spanbroek R, Lottaz C. et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 2010; 115: e10-e19.
    CrossrefPubMedGoogle Scholar
  • 13 Schiraldi M, Raucci A, Munoz LM. et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 2012; 209: 551-563.
    CrossrefPubMedGoogle Scholar
  • 14 Zernecke A, Bot I, Djalali-Talab Y. et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circulation research 2008; 102: 209-217.
    CrossrefPubMedGoogle Scholar
  • 15 Drechsler M, Megens RT, van Zandvoort M. et al. Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation 2010; 122: 1837-1845.
    CrossrefPubMedGoogle Scholar
  • 16 Doring Y, Soehnlein O, Drechsler M. et al. Hematopoietic interferon regulatory factor 8-deficiency accelerates atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2012; 32: 1613-1623.
    CrossrefPubMedGoogle Scholar
  • 17 Eash KJ, Means JM, White DW, Link DC. CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood 2009; 113: 4711-4719.
    CrossrefPubMedGoogle Scholar
  • 18 Martin C, Burdon PC, Bridger G. et al. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 2003; 19: 583-593.
    CrossrefPubMedGoogle Scholar
  • 19 Casanova-Acebes M, Pitaval C, Weiss LA. et al. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell 2013; 153: 1025-1035.
    CrossrefPubMedGoogle Scholar
  • 20 Devi S, Wang Y, Chew WK. et al. Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. J Exp Med 2013; 210: 2321-2336.
    CrossrefPubMedGoogle Scholar
  • 21 Bot I, Daissormont IT, Zernecke A. et al. CXCR4 blockade induces atherosclerosis by affecting neutrophil function. J Mol Cell Cardiol 2014; 74: 44-52.
    CrossrefPubMedGoogle Scholar
  • 22 Bernhagen J, Krohn R, Lue H. et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 2007; 13: 587-596.
    CrossrefPubMedGoogle Scholar
  • 23 Klasen C, Ohl K, Sternkopf M. et al. MIF promotes B cell chemotaxis through the receptors CXCR4 and CD74 and ZAP-70 signaling. J Immunol 2014; 192: 5273-5284.
    CrossrefPubMedGoogle Scholar
  • 24 Kowalska MA, Ratajczak J, Hoxie J. et al. Megakaryocyte precursors, megakaryocytes and platelets express the HIV co-receptor CXCR4 on their surface. Br J Haematol 1999; 104: 220-229.
    CrossrefPubMedGoogle Scholar
  • 25 Gear AR, Suttitanamongkol S, Viisoreanu D. et al. Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function. Blood 2001; 97: 937-945.
    CrossrefPubMedGoogle Scholar
  • 26 Kraemer BF, Borst O, Gehring EM. et al. PI3 kinase-dependent stimulation of platelet migration by stromal cell-derived factor 1. J Mol Med (Berl) 2010; 88: 1277-1288.
    CrossrefPubMedGoogle Scholar
  • 27 Chatterjee M, Seizer P, Borst O. et al. SDF-1alpha induces differential trafficking of CXCR4-CXCR7 involving cyclophilin A, CXCR7 ubiquitination and promotes platelet survival. FASEB J 2014; 28: 2864-2878.
    CrossrefPubMedGoogle Scholar
  • 28 Chatterjee M, Borst O, Walker B. et al. Macrophage migration inhibitory factor limits activation-induced apoptosis of platelets via CXCR7-dependent akt signaling. Circ Res 2014; 115: 939-949.
    CrossrefPubMedGoogle Scholar
  • 29 Hillyer P, Mordelet E, Flynn G, Male D. Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration. Clin Exp Immunol 2003; 134: 431-441.
    CrossrefPubMedGoogle Scholar
  • 30 Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res 2007; 100: 158-173.
    CrossrefPubMedGoogle Scholar
  • 31 Dela Paz NG, D’Amore PA. Arterial versus venous endothelial cells. Cell Tissue Res 2009; 335: 5-16.
    CrossrefPubMedGoogle Scholar
  • 32 Molino M, Woolkalis MJ, Prevost N. et al. CXCR4 on human endothelial cells can serve as both a mediator of biological responses and as a receptor for HIV-2. Biochim Biophys Acta 2000; 1500: 227-240.
    CrossrefPubMedGoogle Scholar
  • 33 Melchionna R, Porcelli D, Mangoni A. et al. Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for athero-genesis. FASEB 2005; 19: 629-631.
    CrossrefPubMedGoogle Scholar
  • 34 Feil C, Augustin HG. Endothelial cells differentially express functional CXC-chemokine receptor-4 under the control of autocrine activity and exogenous cytokines. Biochem Biophys Res Commun 1998; 247: 38-45.
    CrossrefPubMedGoogle Scholar
  • 35 Salcedo R, Wasserman K, Young HA. et al. Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells. Am J Pathol 1999; 154: 1125-1135.
    CrossrefPubMedGoogle Scholar
  • 36 Melchionna R, Romani M, Ambrosino V. et al. Role of HIF-1alpha in proton-mediated CXCR4 down-regulation in endothelial cells. Cardiovasc Res 2010; 86: 293-301.
    CrossrefPubMedGoogle Scholar
  • 37 Wagner NM, Bierhansl L, Noldge-Schomburg G. et al. Toll-like receptor 2-blocking antibodies promote angiogenesis and induce ERK1/2 and AKT signaling via CXCR4 in endothelial cells. Arterioscler Thromb Vasc Biol 2013; 33: 1943-1951.
    CrossrefPubMedGoogle Scholar
  • 38 Kobayashi K, Sato K, Kida T. et al. Stromal cell-derived factor-1alpha/C-X-C chemokine receptor type 4 axis promotes endothelial cell barrier integrity via phosphoinositide 3-kinase and Rac1 activation. Arterioscler Thromb Vasc Biol 2014; 34: 1716-1722.
    CrossrefPubMedGoogle Scholar
  • 39 Chen LH, Advani SL, Thai K. et al. SDF-1/CXCR4 signaling preserves microvascular integrity and renal function in chronic kidney disease. PLoS One 2014; 9: e92227.
    CrossrefPubMedGoogle Scholar
  • 40 Zernecke A, Bidzhekov K, Noels H. et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2009; 2: ra81.
    PubMedGoogle Scholar
  • 41 Noels H, Zhou B, Tilstam PV. et al. Deficiency of endothelial Cxcr4 reduces reendothelialization and enhances neointimal hyperplasia after vascular injury in atherosclerosis-prone mice. Arterioscler Thromb Vasc Biol 2014; 34: 1209-1220.
    CrossrefPubMedGoogle Scholar
  • 42 Amin MA, Volpert OV, Woods JM. et al. Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase. Circ Res 2003; 93: 321-329.
    CrossrefPubMedGoogle Scholar
  • 43 Gregory JL, Morand EF, McKeown SJ. et al. Macrophage migration inhibitory factor induces macrophage recruitment via CC chemokine ligand 2. J Immunol 2006; 177: 8072-8079.
    CrossrefPubMedGoogle Scholar
  • 44 Lin SG, Yu XY, Chen YX. et al. De novo expression of macrophage migration inhibitory factor in atherogenesis in rabbits. Circ Res 2000; 87: 1202-1208.
    CrossrefPubMedGoogle Scholar
  • 45 Tillmann S, Bernhagen J, Noels H. Arrest functions of the MIF ligand/receptor axes in athero-genesis. Front Immunol 2013; 4: 115.
    PubMedGoogle Scholar
  • 46 Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004; 84: 767-801.
    CrossrefPubMedGoogle Scholar
  • 47 Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res 2012; 95: 156-164.
    CrossrefPubMedGoogle Scholar
  • 48 Schecter AD, Berman AB, Yi L. et al. HIV envelope gp120 activates human arterial smooth muscle cells. Proc Natl Acad Sci USA 2001; 98: 10142-10147.
    CrossrefPubMedGoogle Scholar
  • 49 Li F, Guo WY, Li WJ. et al. Cyclic stretch upregulates SDF-1alpha/CXCR4 axis in human saphenous vein smooth muscle cells. Biochem Biophys Res Commun 2009; 386: 247-251.
    CrossrefPubMedGoogle Scholar
  • 50 Pan CH, Chen CW, Sheu MJ, Wu CH. Salvianolic acid B inhibits SDF-1alpha-stimulated cell proliferation and migration of vascular smooth muscle cells by suppressing CXCR4 receptor. Vascul Pharmacol 2012; 56: 98-105.
    CrossrefPubMedGoogle Scholar
  • 51 Li LX, Zhang XF, Bai X, Tong Q. SDF-1 promotes ox-LDL induced vascular smooth muscle cell proliferation. Cell Biol Int 2013; 37: 988-994.
    CrossrefPubMedGoogle Scholar
  • 52 Zhang L, Brian L, Freedman NJ. Vein graft neointimal hyperplasia is exacerbated by CXCR4 signaling in vein graft-extrinsic cells. J Vasc Surg 2012; 56: 1390-1397.
    CrossrefPubMedGoogle Scholar
  • 53 Zernecke A, Schober A, Bot I. et al. SDF-1alpha/ CXCR4 axis is instrumental in neointimal hyper-plasia and recruitment of smooth muscle progenitor cells. Circ Res 2005; 96: 784-791.
    CrossrefPubMedGoogle Scholar
  • 54 Akhtar S, Gremse F, Kiessling F. et al. CXCL12 promotes the stabilization of atherosclerotic lesions mediated by smooth muscle progenitor cells in Apoe-deficient mice. Arterioscler Thromb Vasc Biol 2013; 33: 679-686.
    CrossrefPubMedGoogle Scholar
  • 55 Feil S, Fehrenbacher B, Lukowski R. et al. Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ Res 2014; 115: 662-667.
    CrossrefPubMedGoogle Scholar
  • 56 Rong JX, Shapiro M, Trogan E, Fisher EA. Trans-differentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci USA 2003; 100: 13531-13536.
    CrossrefPubMedGoogle Scholar
  • 57 Robbins CS, Hilgendorf I, Weber GF. et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med 2013; 19: 1166-1172.
    CrossrefPubMedGoogle Scholar