Introduction
Circulating endothelial cells (CECs) are exfoliated endothelial cells which have penetrated into peripheral blood. CECs can be isolated from peripheral blood and counted. The elevated level of these cells, which occurs in a variety of diseases and leads to blood vessel damage, is a new and promising diagnostic and prognostic marker. The number of identified diseases that raise endothelial cell levels in peripheral blood has been constantly increasing. This issue has been described in chronic venous insufficiency, Behcet’s disease, septic shock, breast cancer, myeloid leukaemia, lymphoma, inflammatory vascular diseases, Kawasaki disease, systemic lupus erythematosus, scleroderma, diabetes, ischemic heart disease, acute coronary syndromes, abdominal aortic aneurysm, lower extremities ischemia, ischemic stroke, pulmonary hypertension, cytomegalovirus (CMV) infection and Rickettsia Conorii infection, among others.
Circulating endothelial progenitor cells (CEPCs) were first described in 1997. They come from the bone marrow, differ from CECs in terms of phenotypic features, and participate in postnatal neovascularization and reconstruction of the damaged endothelium. CEPCs are released from the bone marrow in response to tissue ischemia (through a variety of factors, including VEGF) and act as a substrate for neoangiogenesis there (fig. 1).
The aim of this study is to present the issue of CECs and CEPCs, their immunological characteristics and methods of determination, as well as selected diseases and clinical conditions in which the level of these cells is connected with their manifestation and/or exacerbation.
Circulating endothelial cells (CECs)
CECs were first identified and described in the 1970s, when a light microscope was used to assess the morphology of peripheral blood smear [1, 2]. Monoclonal antibodies were first applied to identify CECs in 1991.
The immunomagnetic isolation and flow cytometry methods are currently considered the ‘gold standard’ [1, 3]. A study was devised to compare the sensitivity and specificity of the two methods in 2006. In this experiment, Goon et al. showed that the methods of immunomagnetic isolation and flow cytometry are equally valuable and their results consistent. CECs are exfoliated cells, that is vascular endothelial cells separated from the endothelium and expressing the surface receptors CD146 and CD34, but not CD45. In their studies, Rowand et al. examined the levels of CECs in tumour metastases [4] using the receptors CD146+, CD105+ and CD45–. Receptor CD146 may also occur on the surface of CEPCs, tromboblasts, periodontal tissues, malignant tissues (prostate adenoma, melanoma) [2, 5], smooth muscle cells and some activated T cells [4]. The researchers emphasize the lack of standards in the immunological definition of these cells [2, 4]. In the immunomagnetic method, CECs are defined as suitably sized cells that join (in a fluorescent microscope image) 4 or more immunomagnetic beads. Their endothelial origin is confirmed by the expression of receptors for von Willebrand factor (vWF), nitric oxide synthase, selectin-E, and others [5]. According to some authors [5–7], the presence of CECs in peripheral blood is an expression of endothelial damage. According to others [3], their small number in the blood may be caused by natural turnover (endothelial cell turnover). It has been proven that their elevated level correlates with pathological conditions or the exacerbation of certain diseases. The mechanisms by which ECs are separated from the endothelium are poorly understood. They may include apoptosis and proteolysis of subendothelial matrix proteins, and also a direct complement-dependent neutrophil attack in the case of inflammatory diseases [1]. They may also be detached as a consequence of mechanical damage or a deficiency of anchoring proteins (fibronectin, laminin, collagen type IV) [2, 5]. These cells are likely to have the ability to induce an inflammatory response. Holmen et al. [8] showed that CECs obtained from patients with Wegener’s granuloma secrete several chemokines that activate neutrophils (IL-8, ENA-78, MIP-1-alpha, GRO-alpha) and produce the inducible form of nitric oxide synthase [9]. The expression of tissue factor on the surface of CECs is responsible for tissue factor (TF) activation of the dependent coagulation cascade. The origin of CECs (arteries, veins, macro– or microcirculation) remains unclear. Marker CD36 seems to determine the ‘microcirculation’ origin of CECs, while its absence indicates that the large vessel is the origin of the endothelial cells (fig. 2) [2, 5, 10].
Circulating endothelial progenitor cells (CEPCs)
CEPCs were first isolated and described by Asahara et al. in 1997 [11]. Until that time, it was believed that the major mechanism responsible for repairing a damaged endothelium was associated with local migration and proliferation of mature endothelial cells adjacent to the injury site.
It is now a well-known fact that these cells come from the bone marrow [1, 2, 12] and are released in response to stimuli that induce angiogenesis, for example vascular endothelial growth factor (VEGF), chronic ischemia and vascular trauma. Determining peripheral blood CEPCs is problematic since no specific markers of these molecules have been identified. Currently, most authors consider circulating endothelial progenitor cells as co-expression of cell receptors CD34 (marker for hematopoietic stem cells), Flk-1/KDR (or CD309 receptor for VEGF), and TIE-2. Receptors for VEGF, von Willebrand factor, VE-cadherin, and CD146, CD31 are those markers, which seem to confirm the endothelial origin of those cells [12].
The ability of CEPCs to proliferate, migrate and differentiate into mature endothelial cells is an important factor differentiating CECs from CEPCs [2, 3, 5], as is the possibility of in vitro cultivation after isolation from peripheral blood. These properties are not typical of CECs, which become necrotic or apoptotic after being isolated from peripheral blood and are not suitable for cultivation without providing special conditions. Many data [10, 13–16] indicate an inverse relationship between the levels of CECs and CEPCs; an elevated level of CECs is associated with a lower level of CEPCs. However, there are few studies testing the simultaneous levels of CECs and CEPCs.
Methodology for determining CECs and CEPCs
According to Goon et al. [3], the immunomagnetic method is the most popular and widely used method to determine CECs. This involves ‘grabbing’ cells that express CD146 by using magnetic beads coated with anti-CD146 antibodies and combining these complexes with lectins from the gorse Ulex europaeus. This method was first used by George et al. in 1992 [17].
Flow cytometry involves the simultaneous determination of several CECs surface receptors, such as CD146 and CD34, and the lack of CD45 and CD133 (a marker of CEPC immaturity). In order to compare the accuracy and specificity of the two methods, the authors examined the following three groups of patients for the presence of CECs: a healthy control group, patients with acute coronary syndrome and a group of women with primary breast cancer in the preoperative period. The results showed no significant differences in CEC level. The study revealed that there was less agreement between the two methods in the healthy control group than there was in the case of ill subjects. Flow cytometry has been shown to give slightly higher CEC counts, which probably makes it more sensitive in a group of ill subjects. Most importantly, different authors studying various diseases in terms of CECs use slightly different criteria for defining CECs. This is shown in the table 1.
In peripheral blood, CECs are regarded a marker of endothelial damage, while CEPCs are a marker of repair [2, 5, 12, 18, 20]. And vice versa: reduced number of CEPCs in diseases such as diabetes, in-stent restenosis, myocardial infarction and ischemia are negative prognostic factors [18, 21].
Some authors [22, 23] report that the ability to form colonies is a good mean of distinguishing CEPC (capable to form colonies) from CEC (incapable to form colonies). It has been shown that cells that exhibit co-expression of KDR and CD133 differentiate into endothelial cells and can therefore be reliable EPC markers. George et al. [21] studied various CEPC markers and compared them with the level of plasma factors, for example VEGF, erythropoietin (EPO) and C-reactive protein (CRP). These studies showed that the CD34/KDR receptor most significantly correlates with the level of VEGF. This justifies the conclusion that CD34/KDR is the most appropriate receptor for defining CEPCs. Cells expressing CD133/KDR are less mature than those expressing CD34/KDR [5].
CECs in cardiovascular diseases
CECs are rarely found in the peripheral blood of healthy individuals and do not normally exceed 3/ml to 8/ml [1, 4, 5]. Their level in patients with exacerbations is significantly higher than in patients in whom the disease is in remission or regression. It has been proven that in the case of lower limb ischemia, patients with pain at rest have a higher CEC level than those with intermittent claudication [13]. The same applies to the coronary arteries, where the CEC level is higher in patients with acute myocardial infarction (AMI) or unstable angina than in patients with stable angina [5, 10, 13, 28]. CEC level as a marker of endothelial damage correlates with endothelial dysfunction measured as an increase in vWF, TF [5, 13, 28, 29] and CRP [30]. Quilici et al. [31] have shown that simultaneous determination of CECs and troponin in non-ST segment elevation myocardial infarction (NSTEMI) significantly improves the accuracy of AMI diagnosis and that the CEC level is at its highest at the moment of infarction and returns to normal within 8 hours. Mutin et al. [10] have shown that this increase can persist for as long as 18–24 hours after AMI. Similarly, in the case of coronary angioplasty, the normalized CEC level before the procedure increases after angioplasty and remains elevated for 4 hours after the surgery [10, 17].
A tripling of the CEC level has been demonstrated in heart failure [14]. The level in acute and chronic heart failure was similarly elevated. CEC level has also been confirmed as a predictor of cardiovascular events [29].
Koc et al. [32] found that 7 out of 19 of their patients (haemodialysed) with CEC levels elevated to 19/ml and higher experienced cardiovascular events.
These episodes did not occur in patients with normal CEC levels. Montalescot et al. [33, 34] studied patients admitted due to acute coronary syndromes (ACS). Their elevated levels of CECs and pro-inflammatory cytokine IL-6 and vWF during the first 48 hours after being admitted were the only predictors of major cardiovascular events and death within one month and one year. In this study they demonstrated that the levels of CECs and IL-6 measured during the first 48 hours after the onset of ACS significantly correlate with the presence of major cardiovascular events within one month and one year. They also found the previously described [13, 28] level of vWF as a major predictive factor in cardiovascular events.
CEPCs and diabetes
Before the discovery of CEPCs, the mechanisms responsible for the impairment of neoangiogenesis in this disease were not known. It is now known that abnormalities in the number and the function of CEPCs play an important role in the development and progression of many diabetic complications, including peripheral vascular disease, cardiomyopathy, nephropathy, neuropathy and diabetic retinopathy [35]. The number of CEPCs is also reduced in the presence of risk factors for cardiovascular disease, for example hypercholesterolemia, smoking and chronic renal failure [35–37]. A decrease in CEPCs was reported in diabetes types 1 and 2 [30, 38–40]. Fadini et al. were the first to prove the relationship between peripheral vascular disease (PVD) and low CEPC levels in type 2 diabetes [30]. They tested 51 patients divided into 3 groups: patients with diabetes but without PVD; patients with diabetes and PVD; and patients without diabetes but with PVD. CEPC levels were examined using flow cytometry (surface marker CD34 and KDR-receptor for VEGF). Their study confirmed reduced CEPC levels in patients with diabetes compared to the healthy control group. In addition, they demonstrated that patients with a diabetic foot at the critical ischemia or necrosis stage have even lower CEPC levels than patients with diabetes and PVD but with no necrotic lesions. The impaired development of collateral blood vessels – an important compensatory mechanism in ischemia – is therefore caused by a lack of CEPCs. High glucose levels can stimulate CEPC apoptosis. Their low level is therefore a consequence of impaired mobilization from the bone marrow and short survival time. Churdchomjan et al. [41] compared the number and function of CEPCs in patients with poorly and well-controlled diabetes. They noticed that the total number of CEPCs in diabetic patients was significantly lower than in healthy subjects. Patients with well-controlled diabetes had significantly higher CEPC levels than those with poorly controlled or completely uncontrolled blood glucose. In addition, the authors observed cells during 3 weeks of cultivation. They reported that the cells isolated from healthy individuals did not show any significant morphological differences compared to the cells isolated from patients with diabetes mellitus. However, the cells of diabetics needed three times longer to form a colony compared to the cells of healthy individuals [39, 41]. The researchers also subjected CEPCs to high glucose concentrations and observed their vitality, number, ability to proliferate and predisposition to apoptosis. After several days of cultivation, the number of CEPCs in the tubes with glucose at a concentration of 13.5–19.5 mmol/l was significantly lower than in the tubes with glucose at a concentration of 5.5 mmol/l. The cells subjected to high glucose concentrations had a reduced ability to proliferate, even when the glucose concentration corresponded to that recognized as the limit of proper diabetes control (7.8 mmol/l). The number of apoptotic cells was also significantly higher in samples that had higher glucose concentrations. In another study conducted by Fadini et al. [35], the authors claim that any description of CEPCs should include a quantitative and qualitative assessment of their functions. Flow cytometry is the ‘gold standard’ for quantitative evaluation. A qualitative assessment can include testing the ability to multiply, form colonies (in response to growth factors released locally as a result of vascular injury or ischemia), adhere (necessary in the processes of angiogenesis and reendotelization), migrate through the extracellular matrix (also crucial for the growth of new blood vessels) and adjust to the spatial organization of the vessel (tube formation). According to the authors, the number of CEPCs is decreased in both type 1 and type 2 diabetes. The reduced ability to multiply, adhere, migrate and integrate with the structure of new blood vessels indicates qualitative CEPC impairment in diabetes. The mechanisms responsible for the impaired formation of new blood vessels in diabetes include reduced mobilization from the bone marrow, decreased ability to multiply, and a shortened survival time in peripheral blood. Ischemia is the strongest factor stimulating the release of EPCs into peripheral blood. Hypoxia inducible factor-1 (HIF-1) is consequently created. This indirectly activates VEGF. A reduction of both these factors was noticed by the authors in the cardiac tissue of diabetic patients during acute coronary syndrome [42].
Studies conducted in rats found that a reduction of HIF-1 expression correlated with the extent of myocardial infarction [43–45]. Humpert et al. showed that insulin therapy increases CD34+ and CD133+ levels in decompensated diabetes in rats [46]. The quantity of CEPCs is not only conditioned by their release from the bone marrow, but also by their survival time in peripheral blood. It was found that factors such as oestrogens, statins and exercise inhibit the apoptosis of CEPCs, while C-reactive protein and hypoxia stimulate it. In animal models, diabetic angiopathy was prevented by implanting endothelial progenitor cells (EPCs) taken from healthy animals. In these models, ‘diabetic’ EPCs were not only able to conduct angiogenesis, but also exhibited anti-angiogenetic properties [44, 45]. The replacement of diabetic EPCs by a pool of cells taken from healthy animals significantly accelerated wound healing in diabetics. Yoon et al. [47] demonstrated that diabetic cardiomyopathy is characterized by an early and progressive decrease in VEGF expression (myocardial). This reduces blood density, induces fibrosis and impairs cardiac muscle contractility. Rats with diabetic cardiomyopathy also had low CEPC levels. The authors put forward the hypothesis that diabetic cardiomyopathy is a complex microvascular complication, where a deficit of CEPCs is a leading cause of microvascular network ‘dilution’ and thus critically disables myocardial perfusion [44, 45, 47]. It can be presumed that a properly planned intervention in the number of CEPCs and an improvement in their functionality may be important factors in any strategy aimed at treating diabetic complications. Yun-fei Liao et al. [48] studied a group of 46 patients with newly diagnosed type 2 diabetes (and who therefore had not previously been treated) and a group of 51 patients with no history of diabetes and negative oral glucose tolerance test (OGTT) results. The results (the number of CEPCs/ml in blood) correlated with the outcomes of the FMD test(flow-mediated dilation). They found that the number of CEPCs directly correlates with the result of the FMD test in the brachial artery.
The authors studied the same parameters after 16 weeks of treatment with metformin and observed a statistically significant improvement in the number of CEPCs and a greater expansion of the brachial artery in the FMD test. The authors emphasize that the endothelial function (measured using the FMD test) is completely impaired in patients with newly diagnosed diabetes and that using metformin significantly improves it. The absolute number of CEPCs is a significant and independent risk factor for diabetic complications. Reports have appeared on its correlation with other parameters and markers of diabetes in recent years. After examining the level and assessing the function of CEPCs, Loomans et al. concluded that the level of CEPCs is inversely correlated with the level of HbA1c [38].
The authors argue that the role of these cells is not limited to angiogenesis through being incorporated into the structure of new blood vessels, but that they secrete many pro-angiogenetic factors through exocrine activity. It is still not clear whether patients with severe damage to their endogenous CEPC pool will be sensitive to these factors. Nor is it clear whether it is better to transplant a pool of healthy CEPCs or to pharmacologically ‘repair’ these autogenous.
Jin Hur et al. [49] describe two types of CEPCs, which they call ‘early’ and ‘late’ CEPCs. The former are shaped like a spindle, and when cultured in vitro, their growth peaks between the second and third week and they die within 4 weeks. The latter are more oval in shape, multiply most intensively between the fourth and eighth week and die after 12 weeks of cultivation. They also differ in terms of expression of surface receptors such as VE-cadherins, kinase insert domain receptor (KDR) and CD45. ‘Late’ CEPCs synthesize more nitric oxide than ‘early’ CPCs, are more frequently incorporated into the umbilical vein endothelial layer and better adjust to the vascular shape (tube formation). ‘Late’ CEPCs are also more active in terms of angiogenic cytokines synthesis (VEGF, interleukin-8). However, both types of cell have a similar potential to create new blood vessels. The ‘late’ cells are formed during the maturation of the early ones, and therefore belong to the same cell line at different stages of growth.
The role of CEPCs in cardiovascular events
CEPCs are beneficial to peripheral blood. Once released from the bone marrow, they head for endothelial damage sites and help repair it [12]. Schmidt-Lucke et al. [8] assume that the presence of atherosclerotic risk factors is associated with lower CEPC levels. The authors selected a group of 120 subjects: 44 with coronary artery disease; 33 with unstable angina; and 44 healthy individuals as a control group. The control group had a significantly higher CEPC level in their peripheral blood than the subjects with coronary artery disease. Atherosclerosis risk factors, such as age, hypertension, smoking, and family history of heart disease were inversely correlated with the number of CEPCs. Patients who suffered a cardiovascular event during the last 10–12 months of follow-up had a significantly lower CEPC level when they entered the study.
The authors also examined the CEPC level at which people are predisposed to cardiovascular events and the probability of such an event occurring if the CEPC level is lowered. It was observed that reduced levels were connected with a 4-fold increase in the risk of major events during the follow-up period. CEPCs are therefore an independent predictor in the prognosis of acute coronary events.
Urbich [12] reports that CEPCs play a therapeutic role. Implanting CEPCs previously isolated from the bone marrow into the bloodstream of mice after myocardial infarction significantly improved blood flow and reduced scarring of the left ventricle muscle. Additionally, CEPCs support post-natal neovascularization caused by hypoxia and tissue damage. The authors also report that statins, oestrogens and exercise are factors that ‘protect’ from a decrease of CEPCs.
CECs and CEPCs in malignant diseases
The progression of malignant tumours depends on an intensified, non-physiological angiogenesis in order to nourish tumour tissue and disseminate cells. Vascular endothelial cells are stimulated by a number of factors that are particularly active in carcinogenesis, for example cytokines, lipoproteins and oxidative stress. The uncontrolled activation of these factors in malignant tumours leads to endothelial cells losing their integrity and becoming dysfunctional. This can be measured by using plasma markers including vWF, tissue plasminogen activator, E-selectin and thrombomodulin, and by applying the FMD test in the brachial artery. Mancuso et al. were the first to describe elevated CEC levels in malignant diseases [50]. They divided circulating endothelial cells into resting CECs (rCECs) and activated CECs (aCECs).
According to their pioneering study, both fractions are elevated in patients diagnosed with breast cancer or lymphoma. CEPCs also play a role in tumorigenesis, especially in tumour angiogenesis, according to recent studies [51]. Yet another marker has been described in connection with endothelial damage – endothelial microparticels (EMP). These are ‘bubbles’ formed from the endothelial cell membrane detached from them as a result of damage or activation. They express CEC surface markers and may serve as a signal for cytokines and adhesins [2]. Elevated CEC levels have been described in lymphoma, skin melanoma, ganglioma, carcinoid, cancer of the breast, colon, stomach, oesophagus, kidney, ovary, uterine cervix, testicle and prostate, and in malignant tumours of the head and neck. It is not known whether their increased levels result from local damage to tumour vessels or from a generalized process and systemic activation of the endothelium. Mancuso et al. [50] reported higher CEC levels in breast cancer and lymphoma.
These studies show that CEC levels increase in the early stages of the disease and in metastases, but decline after quadrantectomy. Patients with lymphoma in complete remission after chemotherapy ‘attain’ a normalized CEC level. This suggests that CEC level may be a potential tool in monitoring disease progression and recovery. Similarly, Beerepoot et al. [52] found a significant CEC increase in patients with a progressive malignant disease compared to patients in remission.
Zhang et al. [53] studied the effect of treatment with Thalidomide on CEC and EPC levels in patients with multiple myeloma. They first proved elevated CEC and CEPC levels in this disease, and later reported their parallel decline after thalidomide therapy.
The cited studies show that an increase in the CEC level coincides with carcinogenesis. Until recently, it was believed that, in adulthood, new blood vessels are formed by budding from the existing vessels in a process known as angiogenesis. However, more recent studies suggest that postnatal angiogenesis depends on the differentiation of immature progenitor cells from the bone marrow into mature cells [11, 54, 55]. These cells are mobilized and incorporated into places of vascular growth or repair. Their role in malignant diseases is not clear. Some studies show that EPCs derived from bone marrow enhance the formation of tumour vessels by incorporating them into the neoendothelium [56, 57]. Studies conducted in mice demonstrate that such incorporation only occurs in 20–50% [58]. Elevated CEC and CEPC levels have also been reported in acute myeloid leukaemia. Wierzbowska et al. [59] divided circulating endothelial cells into rCECs (defined as CD31+, CD34+, CD146+, CD45–, CD133– and CD105– and CD106– with the last two defined as activation markers), aCECs (surface receptors different only in terms of CD105+ and CD106+) and the CEPCs (CD45–, CD34+, CD31+, CD133+). The level of all fractions was significantly elevated in patients with acute myeloid leukemia (AML) compared to the control group. The authors observed that the CEC level was twice as high in patients with elevated white blood cell count (WBC) and high-density lipoprotein (HDL). The level of rCECs, aCECs and CEPCs after the first course of chemotherapy was significantly lower than when AML was diagnosed. Identified and counted endothelial cells may come from vascularization foci or other sites distant from the tumour, after prior activation by cytokines released from the tumour or mobilized from the bone marrow.
CEPCs were also examined in non-small cell lung cancer. A pioneering study on this subject [60] reported a higher level of CEPCs in patients before treatment and a correlation between a high CEPC level and a poor prognosis. The authors show that the CEPC level decreased significantly in patients who responded well to treatment. This makes CEPC level a good tool for monitoring treatment in proliferative diseases.
CECs and CEPCs in systemic connective tissue diseases
Systemic connective tissue diseases are associated with non-physiological angiogenesis in certain affected areas. Studying a group of 18 patients with rheumatoid arthritis, Ruger et al. [58] demonstrated the presence of cells expressing CD34 and CD133 in the synovial membrane. These cells are grouped just below the synovial membrane. Furthermore, they expressed receptor CXCR-4 for chemokines and VEGFR-2 for vascular growth factor. Hirohata et al. [61] collected progenitor cells from the bone marrow of 13 patients with rheumatoid arthritis (RA) and incubated them in the presence of colony-stimulating factor (CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cells from patients with RA had a significantly higher expression of a receptor for vWF than the cells taken from the bone marrow of healthy individuals. This proves that cells expressing C34 and CD133 are involved in neovascularization of the synovial membrane and progression of the disease. The observations of the synovium are inversely related to the presence of CEPCs in peripheral blood. Grisar et al. [62] examined CEPC levels in 52 patients with rheumatoid arthritis and in 16 patients from the control group and concluded that ill subjects have lower CEPC levels than healthy individuals. CEPC levels in patients whose symptoms were less severe or in remission were similar to those in healthy individuals from the control group. Patients treated with inflimaxib responded to the therapy with an increased CEPC level in their peripheral blood. Therefore, it was concluded that reduced eosinophil cationic protein (ECP) levels in the peripheral blood of patients with RA may be associated with a decreased ability to revascularize hypoxic tissue and may cause cardiovascular events, which are very common in patients with RA.
Testing CEPC and CEC levels in scleroderma confirmed their role as a pathogenic factor and a predictor. Del Papa et al. [63] studied a group of 22 patients with a localized form of scleroderma and 24 patients with a generalized form. The average age was 56 years. Elevated CEC levels were reported in both groups compared to the control group. The level significantly correlated with the activity of disease [64]. The authors divided CECs into passive (at rest) and activated (defined by the expression of receptors CD106 and CD62). The activated CEC level was higher in patients with an active, acute phase of the disease, including patients with pulmonary hypertension, which is a serious complication of scleroderma. The CEPC level was significantly elevated in patients at the early stage of the disease.
Systemic lupus erythematosus (SLE) is a disorder commonly associated with a high risk of developing cardiovascular disease. A diagnosis of SLE is the strongest predictor of cardiovascular disease, even in patients with well-controlled risk factors. Clancy et al. [65] demonstrated that the CEC level in patients with SLE was significantly elevated compared to the control group. The activation of CECs in SLE suggests that these cells may be potential participants of inflammatory processes in response to immunological stimul and work in a kind of vicious circle to induce progressive, inflammatory vascular damage. Inflammatory vascular damage occurs for example in Kawasaki disease, which is described as inflammation of the small, medium and large arteries, especially the coronary vessels. Nakatani et al. [66] assume that the elevated CEC levels observed in the course of this disease are caused by disorders and an impairment of the coronary arteries promoted by the disease. They studied 20 patients with Kawasaki disease and 10 healthy children. The CEC level was about 6/ml in healthy individuals. However, it was significantly increased in patients with Kawasaki disease in acute form, sub-acute form and remission (in descending order). At the same time, it was noted that the CEC level was considerably higher in patients with coronary artery impairment. There was no CEPC growth in the group of healthy individuals, whereas Nakatani reported an elevated CEPC level in 11 of the 20 children with the disease.
Summary
There are increasingly fewer diseases in which the issue of CECs and CEPCs are not described. The PubMed database has more and more items appearing under the entry ‘CECs and CEPCs’ every month. There are also more reports postulating a significant role for CECs and CEPCs as prognostic markers. Isolating autologous endothelial progenitor cells from bone marrow and implanting them into ischemic muscle significantly improves blood flow. This is evident in for example scientific reports claiming significantly faster and better healing of ischemic ulcers.
From these facts it can be concluded that we can expect a breakthrough in diagnosis andtreatment using the described endothelial cells in the very near future.
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Adres do korespondencji:
prof. nadzw. dr hab. n. med. Jacek Wroński
Katedra i Klinika Chirurgii Naczyń i Angiologii
Uniwersytet Medyczny w Lublinie
ul. Staszica 11, 20–089 Lublin
e-mail: jacek.5996069@interia.pl
Acta Angiol Vol. 20, No. 1 pp. 1–18
Copyright © 2014 Via Medica
ISSN 1234–950X
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