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European Journal of Heart Failure 2006 8(2):167-172; doi:10.1016/j.ejheart.2005.06.010
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© 2006 European Society of Cardiology

Increased circulating endothelial cells in acute heart failure: Comparison with von Willebrand factor and soluble E-selectin

Aun Yeong Chong, Gregory Y.H. Lip, Bethan Freestone and Andrew D. Blann*

Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital Birmingham B18 7QH, United Kingdom

* Corresponding author. Tel./fax: +44 121 507 5076. E-mail address: a.blann{at}bham.ac.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 References
 
Background: Circulating endothelial cells (CECs) in the peripheral blood, probably representing the most direct evidence of endothelial cell damage, are increased in myocardial infarction, unstable angina and critical limb ischaemia. As chronic heart failure is also associated with endothelial abnormalities, we hypothesised that CECs are raised in acute heart failure and that they would correlate with plasma indices of endothelial perturbation, that is, von Willebrand factor (vWf) and soluble E-selectin.

Methods: We studied 30 patients with acute heart failure (venesected within 24 h of emergency hospital admission), 30 patients with chronic stable heart failure (venesected as out-patients, all patients in sinus rhythm with ejection fraction ≤40%) and 20 healthy controls. CECs were quantified using epifluorescence microscopy after CD146-immunomagnetic separation and phenotyped by streptavidin/biotin immunocytochemistry. Citrated plasma was analysed for soluble E-selectin and vWf by ELISA.

Results: Levels of CECs, vWf and soluble E-selectin were significantly higher (all p<0.01) in patients with heart failure compared to controls, with no significant differences between acute and chronic heart failure. CECs correlated with plasma vWf (p<0.0001) and soluble E-selectin (p=0.022) but not ejection fraction or NYHA class. In multiple regression analysis, heart failure was the only independent predictor of raised CECs (p<0.0001). Immunoperoxidase-defined surface expression of CD34, CD45 and CD36 by CECs was <2%, 0% and 8%, respectively.

Conclusion: CECs, a possibly heterologous population, may be used as a novel measure of endothelial damage in acute heart failure and may have implications for the thrombotic risk associated with acute and chronic heart failure and prognosis in this condition.

Key Words: Circulating endothelial cells • von Willebrand factor • Soluble E-selectin • Heart failure • Endothelium

Received December 31, 2004; Revised April 21, 2005; Accepted June 28, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Discussion
 References
 
Good endothelial function and integrity are of undoubted importance in cardiovascular disease, including chronic heart failure, and can be assessed by physiological techniques such as flow-mediated dilatation and changes in specific plasma markers (e.g. von Willebrand factor, vWf) [1,2]. Increased numbers of circulating endothelial cells (CECs) in the peripheral blood are present in various pathological conditions involving severe endothelial perturbation, including inflammatory disease, acute myocardial infarction, chronic stable heart failure, unstable angina and critical limb ischaemia, but not in angina or intermittent claudication compared to healthy controls [3-6]. Since CECs are rare in the blood of healthy persons, increased levels imply the most severe form of blood vessel injury, (i.e. that removes adherent endothelial cells from the internal elastic lamina). It follows that desquamated and detached CECs imply that areas of the endothelium are denuded, thus exposing the underlying prothrombotic sub-endothelial layer to the circulating blood. As a consequence, this may activate platelets and the coagulation cascade and be partly responsible for the prothrombotic or hypercoagulable state in these conditions. Indeed, this, in turn, may contribute to the high morbidity and mortality [7,8].

However, CECs are not the only index of endothelial pertubation. As indicated, plasma vWf (a marker of endothelial damage/dysfunction) is increased in all major risk factors for atherosclerosis and in clear atherosclerotic disease (including heart failure) and increased levels also predict poor long-term outcome [9,10]. An alternative endothelial cell plasma marker, soluble E-selectin (possibly reflecting inflammatory endothelial activation), is also raised in numerous cardiovascular diseases although the data on its ability to predict adverse cardiovascular events is not as convincing [4,11,12]. Both vWf and soluble E-selectin have been shown to be abnormal in chronic stable heart failure [13,14].

Thus, there is considerable evidence of abnormal endothelial function in chronic stable heart failure [6,8,13,14]. We therefore hypothesised that CECs are also raised in acute heart failure and that they correlate with established plasma indices of endothelial perturbation (i.e. vWf and soluble E-selectin). To test this hypothesis, we conducted a cross-sectional study of patients with acute onset heart failure who were compared to patients with chronic stable heart failure and to healthy age- and sex- matched controls. We also performed immunocytochemistry to phenotype these CECs.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Discussion
 References
 
2.1. Subjects
We recruited 30 patients with acute heart failure, 30 patients with chronic heart failure and 20 healthy controls. Clinical characteristics of patients and controls are summarised in Table 1. Heart failure was defined according to the European Society of Cardiology guidelines [15]. Acute heart failure patients were recruited and venesected within 24 h of hospital admission and had radiographic evidence of pulmonary oedema, as well as clinical evidence of heart failure. Therefore in virtually all cases, pharmacotherapy had already commenced. Chronic heart failure was defined as patients being in a stable NYHA class for at least 3 months and were recruited from out-patient clinics. All heart failure patients were in sinus rhythm and had documented left ventricular ejection fraction of ≤40% either by M-mode echocardiography or Simpson's method in the presence of significant regional wall motion abnormality. Patients were also classified according to the New York Heart Association (NYHA) criteria, with I-II being mild symptoms and III-IV being moderate to severe symptoms. Patients with acute heart failure were studied within 24 h of admission of hospital, whereas the (entirely separate) cohort of patients with chronic heart failure was studied in our out-patient research clinic. The study protocol was approved by the West Birmingham Research Ethics Committee and all patients gave written informed consent to the study according to the Declaration of Helsinki.


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  		Table 1 Baseline characteristics of study population

 
Exclusion criteria were concomitant atrial fibrillation, acute coronary syndromes (hospital admission for acute myocardial infarction or unstable angina in the previous 3 months), infection or pyrexial illness, recent (<3 months) myocardial infarction or stroke, chronic and systemic illnesses (including renal failure, hepatic impairment, cancer, inflammatory connective tissue disease and inflammatory bowel disease), past history of thromboembolism and the use of oral steroids and hormone replacement therapy. Some of the patients were on warfarin because of left ventricular thrombus, echocardiographic contrast or large regional wall motion abnormality. Healthy control subjects were recruited from amongst healthy hospital staff, spouses of patients and from subjects attending hospital for hernia repair, varicose vein procedures or other relatively minor operations. All healthy control subjects had no clinical evidence of vascular, metabolic, neoplastic, diabetic or inflammatory disease on careful history, examination and routine laboratory tests. None were taking prescription medicines.

2.2. Laboratory
Citrated plasma was obtained from venous blood by centrifugation at 3000 rpm (1000 xg) for 20 min at 4 °C. Aliquots of citrated plasma were stored at –70 °C to allow batch analysis. Soluble E-selectin was measured by ELISA with R and D Systems reagents (Abingdon, UK), with a minimum sensitivity of 1.6 ng/mL. vWf was measured by an established ELISA (Dako, Ely, UK), with a minimum sensitivity of 5 IU/dL. The intra-assay coefficient of variation was <5% and inter-assay variation was <10%.

Blood for CECs was collected in a sodium fluoride tube, prepared for immunomagnetic separation within 1 h and counted by a single observer under epifluorescence microscopy (Zeiss, Welwyn Garden City, UK). The detailed methodology for capturing CECs and criteria for counting CECs have been widely described [3-6]. Briefly, we defined a CEC primarily as an autofluorescent event with cell-like morphology binding a minimum of 4 magnetic beads coated with a monoclonal antibody to CD146 and having a diameter of at least 20 µM (perhaps 4 beads in size). However, other objects, whose morphology was not classically cell-like but were clearly not artefacts, were also identified. In order to be defined as a CEC, an object without a clear cell-like morphology (i.e. possibly a cell carcase) had to bind 10 or more beads. CECs are also present in sheets or clumps binding numerous beads. In such cases, the final number of CECs is determined by approximating the number of 4-bead diameters. Intra- (n=40 determinations) and inter-assay (n=20) coefficients of variation were <5% and <10%, respectively; the inter- and intra-observer variations of the method in our laboratory were <5% [4]. All laboratory work was performed in blinded fashion with respect to the identity of the samples.

CECs were stained by indirect immunocytochemistry by standard techniques at room temperature. Briefly, CECs were air dried to glass slides and re-hydrated in phosphate-buffered saline (PBS) plus 10% normal swine serum (Dako, Ely, UK) for 10 min. Following a PBS wash, a 1/50 dilution of monoclonal antibodies (all Becton Dickinson, Oxford, UK) to CD34 (marking bone marrow-derived progenitor stem cells), CD36 (the thrombospondin receptor, marking microvascular endothelial cells, platelets and monocytes/macrophages) or CD45 (the leukocyte common antigen) was applied to different slides for an hour, followed by a PBS wash. Colour was developed by the Dako LSAB-2 System (Dako, Ely, UK), using first a 10-min biotin step, washes, a 10-min streptavidin step, washes, and 5 min of diaminobenzidine substrate. Slides were washed and taken through alcohol to xylene and mounted under a coverslip. Auto-fluoresence was retained: positive cells stained black. Positive controls were normal Ficoll-prepared (Sigma Aldrich, Poole, UK) peripheral blood mononuclear cells.

2.3. Power calculations
We have previously reported increased CECs in the plasma of 26 subjects with acute myocardial infarction (AMI) and 33 with unstable angina compared to 13 with stable angina and 14 healthy controls with an overall F statistic of 16 giving a p value of <0.001[3]. More recently we found raised levels in 30 chronic heart failure patients compared to 20 controls [6]. Consequently, we hypothesised similar levels and distribution in acute heart failure compared to chronic heart failure and versus healthy controls. Thus, with three groups, our power calculation required a minimum of 20 subjects per group to generate a similar F statistic at p<0.001. This target number of subjects (n=60) provides the power to detect a correlation coefficient (r) of 0.35 at p<0.05 and 1–β=0.85.

2.4. Statistical analysis
Data were analysed by the Shapiro-Wilks test to determine distribution. Normally distributed data are expressed as mean and standard deviation. As the data for left ventricular ejection fraction (LVEF), sE-selectin and CECs were not normally distributed, values were expressed as median (inter-quartile range, IQR). Baseline cross-sectional data among acute heart failure, chronic heart failure and healthy controls were analysed by ANOVA, Mann-Whitney or Kruskal-Wallis test as appropriate, with between-group comparisons by Tukey's post-hoc test and, if appropriate, after log transformation. Categorical data were compared using chi-squared test. Correlations were performed using Spearman's rank correlation method. Multivariate analysis was performed by stepwise multiple regression analysis using CEC as the dependent variable and clinical variables (e.g. age, gender, hypertension, coronary artery disease, etc.) and the presence/absence of heart failure as predictors.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Discussion
 References
 
3.1. Cross-sectional analysis
Median number of CECs were significantly increased (approximately three-fold) in both acute and chronic heart failure compared to healthy controls, with no significant difference between patient groups [Table 2]. Similarly (as expected), mean vWf and median soluble E-selectin levels were also both raised in both patients groups, but (unexpectedly) there was no difference between the two heart failure patient groups. Taking the mean plus two standard deviations to be the top of the normal range, then the top of the normal range for (normally distributed) vWf was exceeded by 21 of the 30 patients (70%) with chronic heart failure and by 15 of the 30 patients (50%) with acute heart failure. Similarly, taking the top of the normal range to be the 95th percentile for soluble E-selectin and CECs (as both are non-normally distributed), then 8 patients (27%) with chronic heart failure and 11 (37%) patients with acute heart failure had raised levels of soluble E-selectin, whilst 22 patients (73%) in both heart failure groups had high levels of CECs.


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  		Table 2 Circulating endothelial cells, von Willebrand factor and soluble E-selectin in heart failure patients and controls

 
3.2. Correlations
In the whole study group, CECs correlated well with vWf (Spearman, r=0.463; p<0.0001, Fig. 1) and modestly with soluble E-selectin (r=0.256; p=0.022). We are under-powered to perform other un-hypothesised sub-group analyses, e.g. for the effects of different therapies, hypertension, smoking, diabetes or ischaemic heart disease. For the same reason, we have not performed a formal sensitivity/specificity analysis. However, in stepwise multiple regression analysis of the entire study group, only heart failure was an independent predictor of raised CECs (p<0.0001).


Figure 1
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  		Fig. 1 Relationship of von Willebrand factor (IU/dl) and circulating endothelial cells (cells/ml). Spearman correlation, r=0.463; p<0.0001.

 
3.3. Characteristics of CECs
Fig. 2 shows a typical, single CEC binding to seven immunobeads and a small contaminant. Immunophenotyping of 124 CECs from patients with heart failure found <2% to co-stain for progenitor cell marker CD34 and 8% to co-stain for microvascular marker CD36. None stained for the leukocyte-common antigen CD45.


Figure 2
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  		Fig. 2 A circulating endothelial cell rosetting with 7 immunobeads.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
References
 
Heart failure is a leading cause of mortality and hospital admissions [16] and patients hospitalized for acute and decompensated heart failure are at particularly high risk of death, with up to 30% inpatient mortality and nearly one-half of patients being re-admitted within 6 months [17,18]. The causes of death in acute heart failure are largely cardiac in origin, but pulmonary embolism and ischaemic strokes account for up to 20% of non-cardiac deaths [19]. While cardiac deaths usually result from lethal arrhythmias, both epidemiological and autopsy results suggest that acute intra-coronary thrombotic occlusion may be the probable triggering event [20-22]. Acute heart failure patients can therefore be regarded to be at high risk of thrombosis-related complications. Indeed, the components of Virchow's triad are fulfilled in heart failure, with abnormalities of flow (poor cardiac function), vessel wall (endothelial damage/dysfunction) and blood constituents and with significant abnormalities of haemostatic factors and platelet function [5,7].

The present study extends the demonstration of raised CECs in acute myocardial infarction, chronic stable heart failure and critical limb ischaemia [3,4,6] to include acute heart failure and also shows that increased CECs correlate with two other markers of endothelial perturbation, i.e. plasma vWf and soluble E-selectin [8-12]. Our previous work in peripheral atherosclerosis and chronic heart failure demonstrated a correlation between CECs and vWf [4,6], findings that may have implications for the thrombotic risk associated with heart failure and poor prognosis in this condition. Indeed, as CECs represent the most direct evidence of endothelial damage, it is not surprising to find increased numbers in heart failure, in view of the extensive evidence of endothelial perturbation in this condition [6-8,13,14]. However, we expected all three endothelial markers to be higher in acute heart failure (requiring hospital admission) compared to (out-patient) chronic stable heart failure. That this did not occur is puzzling and may represent a limitation of our approach or relatively small numbers of subjects with wide distribution and/or the effects of different treatments and co-morbidities. Alternatively, it may represent the upper limit of CECs that are compatible with life. Thus we conclude that the degree of endothelial perturbation is similar between heart failure groups, regardless of ‘acute/chronic’ status.

There is, at present, interest in both CECs and circulating endothelial progenitor cells (EPCs, originating from the bone marrow [23,24]). In our hands, CECs from patients with peripheral atherosclerosis are largely CD34 negative and are thus unlikely to be part of the EPC ‘family’ that bears this marker [24]. Furthermore, using exactly the same methodology, 93% of CECs from patients with acute coronary syndromes stained positive for endothelial nitric oxide synthase [25]. The present study of CECs from patients with heart failure found <2% to stain for CD34, again suggesting very few are EPCs. However, 8% stained positive for the microvascular cell marker CD36 [26,27], suggesting most CECs arise from large vessels. No cells stained for the leukocyte common antigen CD45 confirming the non-leukocyte nature of our CECs.

There is also some debate as to whether or not the CECs captured by this technique are apoptotic or non-apoptotic [3,28,29]. It is possible that the method may be capturing apoptotic cells in the early stages not detected by TUNEL staining [3]. However, the fact that these circulating cells (if still viable) are no longer attached to the basement membrane means that they will undergo apoptosis eventually [28]. Certainly, in vitro studies show that apoptotic human umbilical vein endothelial cells become procoagulant by increased expression of phosphatidylserine and the loss of anticoagulant membrane components [30]. Moreover, these ‘desquamated’ CECs indirectly suggest that the underlying prothrombotic subendothelial surface is exposed to the circulating blood resulting in activation of the coagulation cascade.

Whatever the origin or status of the CECs, the fact of increased numbers implies gross endothelial insult, although the immediate basic pathological event(s) responsible for this is/are unclear. Recent work supports the hypothesis that high shear stress in pulmonary hypertension could result in shedding of the involved endothelial cells, resulting in increased numbers of CECs [31]. The same study reported that 23% of CECs stained positive for E-selectin, implying a low degree of endothelial activation, compared to 7% of CECs from normal volunteers staining for this marker. This paper, like our present report, also showed an overlap between CECs in health and in disease, indicating the need for caution in interpreting causality or in additional assessment. Nevertheless, as raised vWf predicts poor outcome [9,10,14,25] and correlates with CECs (see Refs. [4,6] and, also, present data), it could be that the latter may also be useful in predicting those patients at risk of serious cardiovascular events and therefore worthy of more focussed care. Indeed, in acute coronary syndromes, increased CECs predict poor outcome at 30 days and 1-year follow up [25].

In conclusion, peripheral blood CECs are a relatively novel tool to assess endothelial damage in cardiovascular, autoimmune, cancer and other conditions, although they may be a collection of cells with different phenotypes [3-6,31-33]. However, CECs are arguably the most direct evidence of endothelial damage in vivo. In heart failure, such endothelial damage (possibly induced by pathological processes such as hypoxia and/or increased oxidative stress) may play a role in the pathophysiology of the associated prothrombotic state.


   Acknowledgement
 
We acknowledge the support of the Sandwell and West Birmingham Hospitals NHS Trust Research and Development Programme for the Haemostasis Thrombosis and Vascular Biology Unit and James Devey for immunophenotyping staining.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 References
 

  1. Cines D.B., Pollak E.S., Buck C.A., et al. Endothelial cells in physiology and in the pathophysiology of vascular diseases. Blood (1998) 91:3527–3561.[Free Full Text]
  2. Chong A.Y., Blann A.D., Lip G.Y.H. Assessment of endothelial damage and dysfunction: observations in relation to heart failure. Quart J Med (2003) 96:253–267.[Free Full Text]
  3. Mutin M., Canavy I., Blann A., Bory M., Sampol J., Dignat-George F. Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells. Blood (1999) 93:2951–2958.[Abstract/Free Full Text]
  4. Makin A.J., Chung N.A.Y., Silverman S.H., Blann A.D., Lip G.Y. Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Eur Heart J (2004) 25:371–376.[Abstract/Free Full Text]
  5. Clancy R., Marder G., Martin V., Belmont H.M., Abramson S.B., Buyon J. Circulating activated endothelial cells in systemic lupus erythematosus: further evidence for diffuse vasculopathy. Arthritis Rheum (2001) 44:1203–1208.[CrossRef][Web of Science][Medline]
  6. Chong A.Y., Blann A.D., Patel J., Freestone B., Hughes E., Lip G.Y. Endothelial dysfunction and damage in congestive heart failure. Relation of flow-mediated dilation to circulating endothelial cells, plasma indexes of endothelial damage, and brain natriuretic peptide. Circulation (2004) 110:1794–1798.[Abstract/Free Full Text]
  7. Lip G.Y.H., Gibbs C.R. Does heart failure confer a hypercoagulable state? Virchow's triad revisited. J Am Coll Cardiol (1999) 33:1424–1426.[Free Full Text]
  8. Gibbs C.R., Blann A.D., Watson R.D., Lip G.Y.H. Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm. Circulation (2001) 103:1746–1751.[Abstract/Free Full Text]
  9. Thompson S.G., Kienast J., Pyke S.D.M., Haverkate F., van de Loo J.C.W. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. New Engl J Med (1995) 332:635–641.[Abstract/Free Full Text]
  10. Jansson J.H., Nilsson T.K., Johnson O. von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J (1991) 66:351–355.[Abstract/Free Full Text]
  11. Roldán V., Marín F., Lip G.Y.H., Blann A.D. Soluble E-selectin in cardiovascular disease and its risk factors: a review of the literature. Thromb Haemost (2003) 90:1007–1020.[Web of Science][Medline]
  12. Pigott R., Dillon L.P., Hemingway I.H., Gearing A.J.H. Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun (1992) 187:584–589.[CrossRef][Web of Science][Medline]
  13. Andreassen A.K., Nordoy I., Simonsen S., et al. Levels of circulating adhesion molecules in congestive heart failure and after heart transplantation. Am J Cardiol (1998) 81:604–608.[CrossRef][Web of Science][Medline]
  14. Chin B.S., Conway D.S., Chung N.A., Blann A.D., Gibbs C.R., Lip G.Y. Interleukin-6, tissue factor and von Willebrand factor in acute decompensated heart failure: relationship to treatment and prognosis. Blood Coagul Fibrinolysis (2003) 14:515–521.[CrossRef][Web of Science][Medline]
  15. The Task Force on Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis of heart failure. Eur Heart J (1995) 20:741–751.
  16. Ho K.L.L., Anderson K.M., Kannel W.B., Grossman W., Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation (1993) 88:107–115.[Abstract/Free Full Text]
  17. Brophy J.M., Deslauriers G., Boucher B., Rouleau J.L. The hospital course and short term prognosis of patients presenting to the emergency room with decompensated congestive heart failure. Can J Cardiol (1993) 9:219–224.[Web of Science][Medline]
  18. Krumholz H.M., Parent E.M., Tu N., et al. Readmission after hospitalisation for congestive heart failure among Medicare beneficiaries. Arch Intern Med (1997) 157:99–104.[Abstract/Free Full Text]
  19. Ackman M.L., Harjee K.S., Mansell G., et al. Cause-specific noncardiac mortality in patients with congestive heart failure—a contemporary Canadian audit. Can J Cardiol (1996) 12:809–813.[Web of Science][Medline]
  20. Bowker T.J., Wood D.A., Davies M.J. Sudden unexpected cardiac death: methods and results of a national pilot survey. Int J Cardiol (1995) 52:241–250.[CrossRef][Web of Science][Medline]
  21. Farb A., Tang A.L., Burke A.P., Sessums L., Liang Y., Virmani R. Sudden coronary death: frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. Circulation (1995) 92:1701–1709.[Abstract/Free Full Text]
  22. Davies M.J. Anatomic features in victims of sudden coronary death. Circulation (1992) 85(suppl_I):I-19–I-24.
  23. Hill J.M., Zalos G., Halcox J.P., et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med (2003) 348:593–600.[Abstract/Free Full Text]
  24. Hristov M., Erl W., Weber P.C. Endothelial progenitor cells. Isolation and characterization. Trends Cardiovasc Med (2003) 13:201–206.[CrossRef][Web of Science][Medline]
  25. Lee K.W., Lip G.Y., Tayebjee M., Foster W., Blann A.D. Circulating endothelial cells, von Willebrand factor, interleukin-6 and prognosis in patients with acute coronary syndromes. Blood (2005) 105:526–532.[Abstract/Free Full Text]
  26. Swerlick R.A., Lee K.H., Wick T.M., Lawley T.J. Human dermal microvascular endothelial but not human umbilical vein endothelial cells express CD36 in vivo and in vitro. J Immunol (1992) 148:78–83.[Abstract]
  27. Petzelbauer P., Bender J.R., Wilson J., Pober J.S. Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture. J Immunol (1993) 151:5062–5072.[Abstract]
  28. Stefanec T. Circulating apoptotic endothelial cells. Blood (1999) 94:1482–1483.[Free Full Text]
  29. Stefanec T. Endothelial apoptosis: could it have a role in the pathogenesis and treatment of disease? Chest (2000) 117:841–854.[Abstract/Free Full Text]
  30. Bombeli T., Karsan A., Tait J.F., Harlan J.M. Apoptotic vascular endothelial cells become procoagulant. Blood (1997) 89:2429–2442.[Abstract/Free Full Text]
  31. Bull T.M., Golpon H., Hebbel R.P., et al. Circulating endothelial cells in pulmonary hypertension. Thromb Haemost (2003) 90:698–703.[Web of Science][Medline]
  32. Woywodt A., Streiber F., de Groot K., Regelsberger H., Haller H., Haubitz M. Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis. Lancet (2003) 361:206–210.[CrossRef][Web of Science][Medline]
  33. Mancuso P., Burlini A., Pruneri G., Goldhirsch A., Martinelli G., Bertolini F. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood (2001) 97:3658–3661.[Abstract/Free Full Text]

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