Circulating endothelial cells

Andrew D. Blann; Alexander Woywodt; Francesco Bertolini; Todd M. Bull; Jill P. Buyon; Robert M. Clancy; Marion Haubitz; Robert P. Hebbel; Gregory Y. H. Lip; Patrizia Mancuso; Jose Sampol; Anna Solovey; Françoise Dignat-George

doi:10.1160/TH04-09-0578

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 93(02): 228-235
DOI: 10.1160/TH04-09-0578

Review Article

Schattauer GmbH

Circulating endothelial cells

Biomarker of vascular disease

Andrew D. Blann

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom

,

Alexander Woywodt

²Department of Medicine, Division of Nephrology, Hannover Medical School, Hanover, Germany

,

Francesco Bertolini

³Division of Haematology-Oncology, European Institute of Oncology, Milan, Italy

,

Todd M. Bull

⁴Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA

,

Jill P. Buyon

⁵Division of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, New York, USA

,

Robert M. Clancy

⁵Division of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, New York, USA

,

Marion Haubitz

²Department of Medicine, Division of Nephrology, Hannover Medical School, Hanover, Germany

,

Robert P. Hebbel

⁶Vascular Biology Centre and Division of Hematology-Oncology-Transplantation, University of Minnesota, Minneapolis, Minnesota, USA

,

Gregory Y. H. Lip

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom

,

Patrizia Mancuso

³Division of Haematology-Oncology, European Institute of Oncology, Milan, Italy

,

Jose Sampol

⁷INSERM 608, Laboratoire d’Hematology et Immunology, UFR Pharmacie, Université de la Méditerranée, Marseille, France

,

Anna Solovey

⁶Vascular Biology Centre and Division of Hematology-Oncology-Transplantation, University of Minnesota, Minneapolis, Minnesota, USA

,

Françoise Dignat-George

⁷INSERM 608, Laboratoire d’Hematology et Immunology, UFR Pharmacie, Université de la Méditerranée, Marseille, France

› Institutsangaben

Abstract

Summary

Recent research has recognised new populations of non-hematopoïetic cells in the blood. One of these, circulating endothelial cells (CECs), often defined by the expression of membrane glycoprotein CD146, are rarely found in the blood in health, but raised numbers are present in a wide variety of human conditions, including inflammatory, immune, infectious, neoplastic and cardiovascular disease, and seem likely to be evidence of profound vascular insult. An additional population are endothelial progenitor cells, defined by the co-expression of endothelial and immaturity cell surface molecules and also by the ability to form colonies in vitro. Although increased numbers of CECs correlate with other markers of vascular disease, questions remain regarding the precise definition, cell biology and origin of CECs. For example, they may be damaged, necrotic or apopototic, or alive, and could possess procoagulant and/or proinflammatory properties. However, since these cells seem to be representative of in situ endothelium, their phenotype may provide useful information. Indeed, whatever their phenotype, there is growing evidence that CECs may well be a novel biomarker, the measurement of which will have utility in various clinical settings related to vascular injury. Despite this promise, progress is impeded by the diversity of methodologies used to detect these cells. Accordingly, results are sometimes inconclusive and even conflicting. Nevertheless, increased CECs predict adverse cardiovascular events in acute coronary syndromes, suggesting they may move from being simply a research index to having a role in the clinic. The objective of the present communication is to condense existing data on CECs, briefly compare them with progenitor cells, and summarise possible mechanism(s) by which they may contribute to vascular pathology.

Keywords

Circulating endothelial cells - von Willebrand factor - E-selectin - tissue factor - CD146

Volltext

Referenzen

References
1 Cines DB, Pollak ES, Buck CA. et al Endothelial cells in physiology and in the pathophysiology of vascular disorders.. Blood 1998; 91: 3527-61.
2 Blann AD. Endothelial cell activation, injury, damage and dysfunction: separate entities or mutual terms?. Blood Coagul Fibrinolysis 2000; 11: 623-30.
3 Dignat-George F, Sampol J.. Circulating endothelial cells in vascular disorders: new insights into an old concept. Eur J Haematol 2000; 65: 215-20.
4 Burger PE, Coetzee S, McKeehan WL. et al Fibroblast growth factor receptor-1 is expressed by endothelial progenitor cells.. Blood 2002; 100: 3527-35.
5 Shi Q, Rafii S, Wu MH. et al Evidence for circulating bone marrow-derived endothelial cells.. Blood 1998; 92: 362-7.
6 Bouvier CA, Gaynor E, Cintron JR. et al Circulating endothelium as an indicator of vascular injury. Thromb Diath Haemorrh 1970; 40 (Suppl) 163-8.
7 Hladovec J, Rossman P.. Circulating endothelial cells isolated together with platelets and the experimental modification of their counts in rats.. Thromb Res 1973; 3: 665-74.
8 Wright HP, Giacometti NJ.. Circulating endothelial cells and arterial endothelial mitosis in anaphylactic shock Br J Exp Pathol 1972; 53: 1-4.
9 Gaynor E, Bouvier CA, Spaet TH.. Circulating endothelial cells in endotoxin treated rabbits. Clin Res 1968; 16: 535 (abstract)
10 Prerovsky I, Hladovec J.. Suppression of the desquamating effect of smoking on the human endothelium by hydroxyethylrutosides.. Blood Vessels 1979; 16: 239-40.
11 Hladovec J, Prerovsky I, Stanek V. et al Circulating endothelial cells in acute myocardial infarction and angina pectoris.. Klin Wochenschr 1978; 56: 1033-6.
12 Hladovec J, Jirka J, Prerozsky I. et al Decrease of endothelaemia during immunosuppression. Biomedicine 1976; 25: 204-6.
13 Hladovec J, Prerovsky I.. Endothelial lesion in hypertension. Cor Vasa 1989; 31: 51-4.
14 Hladovec J, Sommerova Z, Pisarikova A.. Homocysteinaemia and endothelial damage after methionine load. Thromb Res 1997; 88: 361-4.
15 Watanabe T, Tokinaga O.. Multinucleated variant endothelial cell: Its characterization and relation to atherosclerosis. Annals NY Acad Sci 1990; 598: 217-22.
16 Jaffe EA. Cell biology of endothelial cells.. Hum Pathol 1987; 18: 234-8.
17 Percivalle E, Revello MG, Vago L. et al Circulating endothelial giant cells permissive for human cytomegalovirus (HCMV) are detected in disseminated HCMV infections with organ involvement.. J Clin Invest 1993; 92: 663-70.
18 Sbarbati R, de Boer M, Marzilli M. et al Immunologic detection of endothelial cells in human whole blood.. Blood 1991; 77: 764-9.
19 George F, Brisson C, Poncelet P. et al Rapid isolation of human endothelial cells from whole blood using S-Endo1 monoclonal antibody coupled to immuno- magnetic beads: demonstration of endothelial injury after angioplasty.. Thromb Haemost 1992; 67: 147-53.
20 Bardin N, George F, Mutin M. et al S-Endo 1, a pan-endothelial monoclonal antibody recognizing a novel human endothelial antigen.. Tissue Antigens 1996; 48: 531-9.
21 Bardin N, Frances V, Lesaule G. et al Identification of the S-Endo 1 endothelial-associated antigen.. Biochem Biophys Res Comm 1996; 218: 210-6.
22 Solovey AN, Gui L, Chang L. et al Identification and functional assessment of endothelial P1H12.. J Lab Clin Med 2001; 138: 322-31.
23 Solovey A, Lin Y, Browne P. et al Circulating activated endothelial cells in sickle cell anemia.. N Engl J Med 1997; 337: 1584-90.
24 George F, Brouqui P, Boffa MC. et al Demonstration of Rickettsia conorii-induced endothelial injury in vivo by measuring circulating endothelial cells, thrombomodulin, and von Willebrand factor in patients with Mediterranean spotted fever.. Blood 1993; 82: 2109-16.
25 Lefevre P, George F, Durand JM. et al Detection of circulating endothelial cells in thrombotic thrombocytopenic purpura.. Thromb Haemost 1993; 69: 522
26 Mutin M, Canavy I, Blann A. et al Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells.. Blood 1999; 93: 2951-8.
27 Camoin-Jau L, Kone-Paut I, Chabrol B. et al Circulating endothelial cells in Behcet's disease with cerebral thrombophlebitis.. Thromb Haemost 2000; 83: 631-2.
28 Janssens D, Michiels C, Guillaume G. et al Increase in circulating endothelial cells in patients with primary chronic venous insufficiency: protective effect of Ginkor Fort in a randomized double-blind, placebocontrolled clinical trial.. J Cardiovasc Pharmacol 1999; 33: 7-11.
29 Dang A, Wang B, Li W. et al Plasma endothelin-1 levels and circulating endothelial cells in patients with aortoarteritis.. Hypertens Res 2000; 23: 541-4.
30 Kas-Deelen AM, Harmsen MC, De Maar EF. et al Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood.. Kidney Int 2000; 58: 2533-42.
31 Kas-Deelen AM, de Maar EF, Harmsen MC. et al Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection: effect of acute rejection.. J Infect Dis 2000; 181: 721-4.
32 Mutunga M, Fulton B, Bullock R. et al Circulating endothelial cells in patients with septic shock.. Am J Respir Crit Care Med 2001; 163: 195-200.
33 Mancuso P, Burlini A, Pruneri G. et al Resting and activated endothelial cells are increased in the peripheral blood of cancer patients.. Blood 2001; 97: 3658-61.
34 Clancy R, Marder G, Martin V. et al Circulating activated endothelial cells in systemic lupus erythematosus: further evidence for diffuse vasculopathy.. Arthritis Rheum 2001; 44: 1203-8.
35 Popa ER, Kas-Deelen AM, Hepkema BG. et al Donor-derived circulating endothelial cells after kidney transplantation.. Transplantation 2002; 74: 1320-7.
36 Woywodt A, Schroeder M, Gwinner W. et al Elevated numbers of circulating endothelial cells in renal transplant recipients.. Transplantation 2003; 76: 1-4.
37 Butthep P, Rummavas S, Wisedpanichkij R. et al Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumour necrosis factor in thalassemia.. Am J Hematol 2002; 70: 100-6.
38 Woywodt A, Streiber F, de Groot K. et al Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis.. Lancet 2003; 361: 206-10.
39 Nakatani K, Takeshita S, Tsujimoto H. et al Circulating endothelial cells in Kawasaki disease.. Clin Exp Immunol 2003; 131: 536-40.
40 Bull TM, Golpon H, Hebbel RP. et al Circulating endothelial cells in pulmonary hypertension.. Thromb Haemost 2003; 90: 698-703.
41 O’Sullivan SE.. The effects of exercise training on markers of endothelial function in young healthy men. Int J Sports Med 2003; 24: 404-9.
42 Makin A, Chung NAY, Silverman SH. et al Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells.. Eur Heart J 2004; 25: 371-6.
43 Yu X, Hirono KI, Ichida F. et al Enhanced iNOS expression in leukocytes and circulating endothelial cells is associated with the progression of coronary artery lesions in acute Kawasaki disease.. Pediatr Res 2004; 55: 688-94.
44 Woywodt A, Scheer J, Hambach L. et al Circulating endothelial cells as a marker of endothelial damage in allogeneic hematopoietic stem cell transplantation.. Blood 2004; 103: 3603-5.
45 Del Papa N, Colombo G, Fracchiolla N. et al Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis.. Arthritis Rheum 2004; 50: 1296-304.
46 Rajagopalan S, Somers EC, Brook RD. et al Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity.. Blood 2004; 103: 3677-83.
47 Gaynor E, Bouvier CA, Cintron JR.. A technique for locating rare cells in the circulation for ultramicroscopy.. Proc Soc Exp Biol Med 1970; 133: 520-3.
48 Woywodt A, Goldberg C, Scheer J. et al A novel assay for the enumeration of circulating endothelial cells.. Annals Hematol 2004; 83: 491-4.
49 Liu Q, Yan X, Li Y. et al Pre-eclampsia is associated with the failure of melanoma cell adhesion mol- ecule (MCAM/CD146) expression by intermediate trophoblast.. Lab Invest 2004; 84: 221-8.
50 Wu GJ, Peng Q, Fu P. et al Ectopical expression of human MUC18 increases metastasis of human prostate cancer cells.. Gene 2004; 327: 201-13.
51 Seo BM, Miura M, Gronthos S. et al Investigation of multipotent postnatal stem cells from human periodontal ligament.. Lancet 2004; 364: 149-55.
52 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s.. Nature 1993; 362: 8019
53 Swerlick RA, Lee KH, Wick TM. et al Human dermal microvascular endothelial but not human umbilical vein endothelial cells express CD36 in vivo and in vitro.. J Immunol 1992; 148: 78-83.
54 Petzelbauer P, Bender JR, Wilson J. et al Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture.. J Immunol 1993; 151: 5062-72.
55 Lin Y, Weisdorf DJ, Solovey A. et al Origins of circulating endothelial cells and endothelial outgrowths from blood.. J Clin Invest 2000; 105: 71-7.
56 Ingber DE. Integrins: versatility as mechanochemical transducers.. Curr Opin Cell Biol 1991; 3: 841-8.
57 Rüegg C, Yilmaz A, Bieller G. et al Evidence for the involvement of endothelial cell integrin anb3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma.. Nature Medicine 1998; 4: 408-14.
58 Breviario F, Caveda L, Corada M. et al Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an endothelium-specific cadherin.. Arterioscler Thromb Vasc Biol 1995; 15: 1229-39.
59 Re F, Zanetti A, Sironi M. et al Inhibition of anchorage- dependent cell speading triggers apoptosis in cultured human endothelial cells.. J Cell Biol 1994; 127: 537-46.
60 Grefte A, Van Der Giessen M, Van Son W. et al Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection.. J Infect Dis 1993; 167: 270-7.
61 Visser MR, Vercellotti GM, McCarthy JB. et al Herpes simplex virus inhibits endothelial cell attachment and migration to extracellular matrix proteins.. Am J Pathol 1989; 134: 223-30.
62 Visser MR, Jacob HS, Goodman JL. et al Granulocyte mediated injury to herpes simplex virus-infected human endothelium.. Lab Invest 1989; 60: 296-304.
63 Clancy RM, Rediske J, Tang X. et al Outside-in signalling in the chondrocyte. Nitric oxide disrupts fibronectin- induced assembly of a subplasmalemmal actin/rho A/focal adhesion kinase signalling complex.. J Clin Invest 1997; 100: 1789-96.
64 Thompson SG, Kienast J, Pyke SD. et al Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.. N Engl J Med 1995; 332: 635-41.
65 Jansson JH, Nilsson TK, Johnson O. von Willebrand factor, tissue plasminogen activator, and dehy- droepiandrosterone sulphate predict cardiovascular death in a 10-year follow up of survivors of acute myocardial infarction.. Heart 1998; 80: 334-7.
66 Montalescot G, Philippe F, Ankri A. et al Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. French Investigators of the ESSENCE Trial.. Circulation 1998; 98: 294-9.
67 Celermajer DS.. Endothelial dysfunction: Does it matter? Is it reversible?. JACC 1997; 30: 325-3.
68 Widlansky ME, Gokce N, Keaney Jr JF, Vita JA. The clinical implications of endothelial dysfunction.. J Am Coll Cardiol 2003; 42: 1149-60.
69 Felmeden DC, Blann AD, Spencer CGC. et al A comparison of flow mediated dilatation and von Willebrand factor as markers of endothelial cell function in health and in hypertension: relationship to cardiovascular risk and the effects of treatment.. Blood Coag Fibrinolysis 2003; 14: 425-31.
70 Osterud B. Tissue factor: a complex biological role.. Thromb Haemost 1997; 78: 755-8.
71 Combes V, Simon AC, Grau GE, Dignat George F. In vitro generation of endothelial microparticles and possible thrombotic activity in patients with lupus anticoagulant.. J Clin Invest 1999; 104: 93-102.
72 Bombeli T, Karsan A, Tait JF. et al Apoptotic vascular endothelial cells become procoagulant.. Blood 1997; 89: 2429-42.
73 Quilici J, Banzet N, Paule P. et al. Circulating endothelial cell count as a diagnostic marker for non-ST elevation acute coronary syndromes Circulation. 2004; 110: 1586-91.
74 Blann AD, Naqvi T, Waite M, CN McCollum. von Willebrand factor and endothelial cell damage in essential hypertension. Journal of Human Hypertension 1993; 7: 10711
75 Preston RA, Ledford M, Materson BJ. et al Effects of severe, uncontrolled hypertension on endothelial activation: soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and von Willebrand factor.. J Hypertens 2002; 20: 871-7.
76 Friedman R, Mears JG, Barst RJ. Continuous infusion of prostacyclin normalises plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension.. Circulation 1997; 96: 2782-84.
77 Folkman J.. Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nature Med 1995; (01) 27-31.
78 Folkman J, Hahnfeldt P, Hlatky J. Cancer: looking outside the genome.. Nature Rev Mol Cell Biol 2000; 1: 76-79.
79 Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors.. Nature Rev Cancer 2002; 2: 727-39.
80 Solovey A, Gui L, Key NS. et al Tissue factor expression by endothelial cells in sickle cell anaemia.. J Clin Invest 1998; 101: 1899-904.
81 Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor.. J Biol Chem 1994; 269: 26486-91.
82 Gu JM, Katsuura Y, Ferrell GL. et al Endotoxin and thrombin elevate rodent endothelial cell protein C receptor mRNA levels and increase receptor shedding in vivo.. Blood 2000; 95: 1687-93.
83 Clancy R, Sesin C, Kurosawa S. et al Expression of endothelial cell protein C receptor and inducible nitric oxide synthase (iNOS) by circulating endothelial cells (CEC) in systemic lupus erythrematosus (SLE). 2003; 48: S374 Abstract
84 Esmon CT. Crosstalk between inflammation and thrombosis.. Maturitas 2004; 47: 305-14.
85 Adams V, Lenk K, Linke A. et al Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia.. Arterioscler Thromb Vasc Biol 2004; 24: 684-90.
86 Hill JM, Zalos G, Halcox JP. et al Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.. N Engl J Med 2003; 348: 593-600.
87 Peichev M, Naiyer AJ, Pereira D. et al Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors.. Blood 2000; 95: 952-8.
88 Vasa M, Fichtlscherer S, Aicher A. et al Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.. Circ Res 2001; 89: E1-7.
89 Verma S, Kuliszewski MA, Li SH. et al C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease.. Circulation 2004; 109: 2058-67.
90 Bompais H, Chagraoui J, Canron X. et al Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells.. Blood 2004; 103: 2577-84.
91 Asahara T, Murohara T, Sullivan A. et al Isolation of putative progenitor endothelial cells for angiogenesis.. Science 1997; 275: 964-7.
92 Rosenweig A. Endothelial progenitor cells.. New Engl J Med 2003; 348: 581-2.
93 Stevens T, Rosenberg R, Aird W. et al NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases.. Am J Physiol Cell Physiol 2001; 281: C1422-33.
94 Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration.. Nat Med 2003; 9: 702-12.
95 Lee KW, Lip GY, Tayebjee M. et al Circulating endothelial cells, Von Willebrand Factor, interleukin- 6 and prognosis in patients with acute coronary syndromes.. Blood 2005; 105: 526-32.