Damage to the vascular endothelium of diabetic patients can be assessed by analysing blood samples for the number of circulating endothelial cells with mitochondrial DNA deletions

1995 ◽  
Vol 23 (3) ◽  
pp. 402S-402S ◽  
Author(s):  
DAVID N. EGAWHARY ◽  
BEN E.P. SWOBODA ◽  
JING CHEN ◽  
FRANK P. VINCE
Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ryan Stone ◽  
David Chaffin ◽  
David Jude ◽  
Zeid Khitan ◽  
Dong Hyun Kim ◽  
...  

Introduction: Endothelial Progenitor cells (EPCs) are bone marrow derived cells that migrate and differentiate into mature endothelial cells and play a significant role in the re-endothelialization and neovascularization of injured endothelium and restoration of vascular function. We examined whether obesity and hypertension exacerbates the levels of biomarkers including circulating endothelial cells (CEC), serum inflammatory cytokines, and the levels of heme oxygenase -1 (HO-1) in EPC. Methods: Peripheral blood from 10 normal, 15 obese, 12 hypertensive, 20 obese-hypertensive and 15 diabetic patients was analyzed for inflammatory cytokines, CEC number, adiponectin and HO-1 levels. Results: The levels of inflammatory cytokines increased with BMI and directly correlated with increasing obesity. Similarly, hypertensive patients have elevated CEC which are further increased in obese hypertensive patients (p<.05). HO-1 was reduced (p<.05) in both hypertensive and obese patients when compared to control. Similarly serum adiponectin levels were lower in hypertensive obese patients when compared to controls (p<.01). Inflammatory cytokines IL-1, IL-6, MCP-1 and TNFα were elevated in obese hypertensive patients compared to non-obese hypertensive patients (p<.05). Conclusion: We demonstrated in hypertension patients that obesity exacerbates vascular dysfunction and increases circulating endothelial cells and inflammatory cytokines. A reduction in the levels of HO-1 and adiponectin imply reduced antioxidant levels which are contributing factors towards vascular and adipocyte dysfunction in hypertension patients. Thus upregulation of HO-1 offers a potential therapeutic approach in the treatment of this population.


2010 ◽  
Vol 162 (4) ◽  
pp. 711-717 ◽  
Author(s):  
Ebru Asicioglu ◽  
Dilek Gogas Yavuz ◽  
Mehmet Koc ◽  
Beste Ozben ◽  
Dilek Yazici ◽  
...  

ObjectiveCirculating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population.MethodsThirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers.ResultsPatients with type 1 diabetes mellitus had higher number of CECs (7.46±5.37 vs 2.13±1.13 cells/ml,P<0.001), lower FMD (7.87±2.19 vs 12.06±2.34%,P<0.001), higher TBARS (4.94±1.20 vs 3.07±0.75 nmol/MDA,P<0.001), lower GSH (206.12±98.06 vs 353.61±68.45 μM,P<0.001), and lower PON activity levels (89.10±17.82 vs 127.65±29.01 U/l,P<0.001) as compared to controls.There was positive correlation between CEC numbers and HbAlc levels (r=0.49,P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r2=0.40,P<0.009) were associated with CEC numbers.ConclusionCECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4900-4900
Author(s):  
Rasmus T. Hoeg ◽  
Dean A. Jobe ◽  
Krista E. Asp ◽  
Steven M. Callister ◽  
Lori A. Meyer ◽  
...  

Abstract Background: Angiogenesis and thrombosis, two conditions associated with perturbation of the vascular endothelium and increased CECs, are frequently observed in PV. We performed this study to quantify and characterize CECs in patients with PV and to determine whether CEC profile is associated with thrombotic complications. We also quantified CEPs in a subgroup of patients. Methods: We used flow cytometry to prospectively analyze CECs and CEPs in the whole blood of healthy patients (n=20) and patients with PV (n=30; 13 treated with hydroxyurea, 12 undergoing phlebotomy alone, and 5 never treated). CECs (CD45−/CD31+/CD146+) were quantified and characterized to determine their apoptotic (annexin stain) or activation (CD106+) states. Cells with CD45−/CD31+/CD133+/VEGF-R2+ immunophenotype were considered CEPs. Results: CEC levels in PV patients were higher compared to healthy controls (median 53 cells/mL [range, 11–392] vs 18.5 cells/mL [range, 4–66]; P&lt; .0001). However, the proportions of apoptotic (17.3% [range, 0–87.5] vs 25.9% [range, 0–57.1]; P= .87) and activated (0.7% [range, 0–28.6] vs 0% [range, 0–57.1]; P= .14) CECs were similar between the two groups. In PV patients with high levels (≥2 SD above control mean or ≥53 cells/mL) of CECs (n=14), 5 (36%) developed thromboses. Four (25%) of 16 PV patients with CEC levels similar to healthy controls developed thromboses. The rates of thrombosis between the groups were not statistically different (P= .69). In addition, CEC count, activation, and apoptosis were similar between the hydroxyurea-treated group and the group not treated with hydroxyurea. We detected low numbers of CEPs in PV patients (n=25) that were similar to controls (4 cells/mL [range, 0–100] vs 8 cells/mL [range, 0–60]; P= .34). Conclusions: CECs, but not CEPs, are significantly increased in PV patients. However, there appears to be no association between CEC number, activation or apoptotic state and the development of thromboses. In addition, hydroxyurea therapy does not appear to effect endothelial cells.


1992 ◽  
Vol 67 (01) ◽  
pp. 147-153 ◽  
Author(s):  
F George ◽  
C Brisson ◽  
P Poncelet ◽  
J C Laurent ◽  
O Massot ◽  
...  

SummaryThe presence in whole blood of circulating endothelial cells (EC) has been a subject of debate for many years. It could represent a good marker of vessel injury. We demonstrate here that human endothelial cells can be directly isolated and identified in circulating blood by means of an endothelial cell specific monoclonal antibody, S-Endol, coupled to micromagnetic beads. The specificity and efficacy of the assay were established using normal blood samples with cultured EC added. Specific rosettes formed between EC and beads could subsequently be isolated with a magnet. The rosetted cells were recovered with a yield >80%. Their endothelial origin was confirmed by the positive labelling of von Willebrand factor and thrombomodulin, as well as the presence of Weibel-Palade bodies. We applied this method to demonstrate significantly increased levels of EC in venous and arterial human blood samples in patients undergoing heart catheterization. This new whole blood immuno-separation method may be useful in determining endothelial cell injury in vascular disorders.


1987 ◽  
Author(s):  
R Musso ◽  
A Longo ◽  
M L Morrone ◽  
R R Cacciola ◽  
A Lombardo ◽  
...  

Increased plasma levels of Fibronectin (Fn),a well known adesive glycoprotein synthesized in vessel endothelial cells, have been reported in diabetes mellitus (DM). Previously, we provided evidence that in type II DM an elevated storage of Fn is present in endothelial cells. We here report that in diabetic subjects an abnormal synthesis of Fn in endothelial cells could also occur. To verify this hypothesis, in 15 patients affected by type II DM, age ranging 36-59, of both sex, without overt clinical vascular complications and in glycometabolic compensation (Hb Alc 8.9 ± 1.5) we evaluated before and after venostasis repeated at several times 30, 60, 90,180 and 210 min the Fn plasma levels. Five healthy volunteers, age and sex comparaf-h ble, were utilized as normal controls. The venostasis were performed at forearm pressure of 10 mmHg over diastolic x 20 min and blood samples were collected from the same vein at the intervals above indicated. Plasma Fn was evaluated by ELISA immuno-enzymatic tecnique using a commercial kit (Biochemia, Milan). The diabetic patients showed after the first venostasis a significant (p<0.001) increase of Fn (317 ± 103μg/ml) versus the baseline values (225±79 μg/ml)while normal controls did not (before 103 ± 37, after 139±61). Such an increase was also seen in EM after the second venostasis ( 298 ±91 μg/ml, vs 128±58 in controls), whereas at third venostasis plasma Fn levels retoumed to the values comparable to the basal ones both in diabetics (245 ±. 88 μg/ml) and in controls (93±41 μg/ml). After 90 min pause by performing the fourth venostasis we observed in diabetics a further increase pf Fn (298±131μg/ml) which reached:again the values noted after the first. No change, on the contrary,was found in the normal group (95±21). In the last venostasis,carried out 30min from the fourth, the plasna Fn lasted significantly (p<0.001.) increased in diabetics (281±107 μg/ml) respect to normal controls (102±19 μg/ml).Our data, therefore, would suggest that in vascular endothelium cf type II DM an increased synthesis of Fn occurs as well.


2010 ◽  
Vol 104 (08) ◽  
pp. 318-326 ◽  
Author(s):  
Michiel Strijbos ◽  
Brigitte van Krimpen ◽  
Reno Debets ◽  
Jaco Kraan ◽  
Stefan Sleijfer ◽  
...  

SummaryCirculating endothelial cells (CEC) are considered a promising marker to determine the extent of vascular damage. However, currently available and validated CEC enumeration assays are laborious, time consuming and costly, which limits their clinical utility. Here, we evaluated the feasibility of quantifying mRNA levels of the endothelium-associated markers CD31, CD144, CD146 and von Willebrand factor (vWf) in peripheral blood (PB) of healthy donors, patients, and human umbilical veins by real-time reverse transcriptase polymerase chain reaction (RTPCR) and their use as surrogate markers for CEC. Whole blood samples and CD146+ cell-enriched fractions were assessed for mRNA and protein expression of CD31, CD144, CD146 and vWf by RT-PCR and flow cytometry, respectively. We showed the feasibility to detect endothelial mRNA isolated from HUVEC numbers as low as 10. However, no endothelial mRNA could be measure in whole blood samples, and only low levels of CD31 and CD146 mRNA were detected in suspensions of isolated CEC with numbers up to 4,450 CEC per sample. We conclude that mRNA levels of CD31, CD144, CD146 and vWf in whole blood as detected by real time RT-PCR cannot be used as biomarkers for endstage endothelial cells such as CEC.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13517-e13517
Author(s):  
María Ángeles Vaz Salgado ◽  
Julie Earl ◽  
Victor Rodriguez Berrocal ◽  
Freddy Salge ◽  
Ana Gomez ◽  
...  

e13517 Background: Glioblastoma (GB) is an aggressive tumor. Circulating Endothelial Cells (CECs) can be detected in peripheral blood and have been related to angiogenesis. CECs have an unclear prognostic value in patients with glioblastoma. The objective of this study was to quantify the presence and number of CECs in GB patients and determine its potential prognostic role. Methods: In this prospective, single center study, peripheral blood samples were obtained at the time of GB diagnosis. For the detection of CECs, 4 ml of blood was analyzed using the CellSearch system (Veridex). CEC blood samples were classified as CD146+, CD105+, CD45− and DAPI+. CEC detection was performed prior to surgery in a total of 26 patients and 22 patients with glioblastoma were included in the final analysis. We mesured progression free survival (PFS) and overall survival (OS). Results: Between 2014 and 2016, twenty two patients with histologically confirmed glioblastoma were studied. There were 14 males and 8 females with an average age of 63 years (range 42-81). A complete resection was achieved in 50% of cases, partial or subtotal resection in 31.8% and biopsy in 18%. The mean number of CECs was 59.3 cells/mL (range 0-954). Patients were classified into two groups depending on the number of CECs: group 1 had a CEC count below the mean and group 2 had a CEC count above the mean. A total of 17 patients (77.2%) were in group 1 and 5 patients (22.7%) were in group 2.The median OS was 14.4 months (range -0.36-33.36) for the entire study population. The median OS was 17.4 months (IC95% 11.47-23.37) for patients in group 1 and 8.12 months for patients in group 2 (IC 95% 4.38-11.85) p = 0.002. The median PFS was 8.94 m (IC95% 5.1-12.69) for group 1 and 3.95 for group 2 (IC 95% 2.91-4.98) p = 0.097. Conclusions: CECs can be detected in recently diagnosed GB patients. The present study demonstrates a possible prognostic value for CEC determination in GB cases at the time of diagnosis.


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