Circulating Endothelial Progenitor Cells Counts Research Articles

The Impact of Modern Anti-Diabetic Treatment on Endothelial Progenitor Cells.

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel's intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin.

“The role of growth medium in the potency of EPC-type 2 diabetes patients” (A study of ALDHbright as a marker of the potency of EPC)

Background & Aim Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease caused by insulin disruption, insulin secretion or both. Hyperglycemia occurs in diabetes, where long-term hyperglycemia causes an increase in oxidative stress, a decrease in antioxidants and an increase in pro-inflammatory factors that contribute to endothelial dysfunction. In these conditions where microenvironment is not right, the amount of available ATP is not adequate, causing a decrease in the number and potential of Endothelial Progenitor Cells (EPC) in playing its function and role in the decreased colonization process. In this preliminary study, the aim was to prove changes in microenvironment by adding growth media to improve the condition of the microenvironment (niche) in an in-vitro able to increase the number and potential of EPC Methods, Results & Conclusion Method: Circulating EPC counts were calculated using a combination of expressions from CD34+ and CD133+ antigen surfaces using BD FACS Canto II flow cytometry, and the potential of EPC was done by adding ALDH bright staining. Then the EPC was isolated and cultured on the growth medium, then cultured for seven days. After that, the number of EPC circulating and the EPC potential is recalculated Result The results of this study indicate that after the addition of growth medium and incubated for seven days, the number of EPCs increased by 413.20%, and 1,401.1% in the controlled and uncontrolled group. Also, the potential of EPC showed by express of ALDHbright was obtained at the end of incubation of 99.9%, in each group in diabetes. Discussion This study illustrates that by adding a growth medium, it can restore microenvironment conditions to be better characterised by the ability of EPC to express bright ALDH which increases very high. Bright ALDH activity shows the ability to re-populating and differentiation and illustrates the operation of retinoids that have a pro-angiogenic effect with modulation of endothelial cell cytokines, the impact of migration and vasculogenesis. Conclusion The addition of growth medium in EPC culture from peripheral blood improves microenviral conditions and can increase the amount of EPC and the potential of EPC associated with its role in the colonisation function.

Abstract P125: Role of Circulating Endothelial Progenitor Cell Levels Predict Cardiovascular Events in Patients on Maintenance Hemodialysis

Background: The number of circulating endothelial progenitor cells (EPCs) has been identified as a surrogate biologic marker for vascular function and cumulative cardiovascular (CV) risk in the general population. Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have markedly decreased EPC counts and function. We hypothesized that the number of circulating EPCs predicts death from all causes and CV events in patients with ESRD on HD. Methods: We quantified the EPCs in blood samples from 70 patients with ESRD on HD. Circulating EPCs were counted by flow cytometry as the number of CD45 low CD34 + VEGFR2 + cells. Death from all causes and CV events served as outcome variables over a median follow-up period of 20 months Results: It has been postulated that the number of circulating EPCs at baseline ranged from 1 to 350 cells per 200 μl, with a mean of ± standard deviation (SD) of 26.0 ± 48.2 cells per 200 μl. The median, lowest and highest tertiles of EPC counts were 11.0, 9.0, and 17.0 cells/200 μl, respectively. Patients with the lowest tertile EPC counts had significantly higher rates of CV events, but mortality was similar between the two groups. After adjusting for these risk factors, HbA1c and the lowest tertile EPC count remained as independent predictors of CV events. A cutoff value of 9.5 cells per 200 μl maximized the power of the EPC count to predict future CV events as determined by ROC curve analysis. Conclusions: Reduced circulating EPC counts independently predicted CV events in 70 patients with ESRD on maintenance HD. Circulating EPCs may play a role in vascular repair, thereby affecting the clinical course of CV events.

Association of endothelial progenitor cells and peptic ulcer treatment in patients with type 2 diabetes mellitus.

The present study aimed to investigate the association between endothelial progenitor cells (EPCs) and peptic ulcers in patients with or without type 2 diabetes mellitus (T2DM), in association with the efficiency of peptic ulcer treatment. The study recruited healthy subjects and peptic ulcer patients with or without T2DM. All the ulcer patients, including those with and without T2DM, were administered omeprazole for 8 weeks. Peptic ulcer patients with T2DM were additionally treated with glipizide and novolin. Blood samples were then obtained from the three groups following ulcer treatment. CD133+ cells were isolated from the blood samples using magnetic bead selection, and cultured in complete medium 199. Morphological and quantity changes in EPCs were observed by light and fluorescence microscopy. In addition, flow cytometric analysis was used to quantify the number of vascular endothelial cells. The treatment was partially effective in 7 of the 32 peptic ulcer patients without T2DM and 12 of the 32 peptic ulcer patients with T2DM. However, this treatment was ineffective in 20 of the 32 peptic ulcer patients with T2DM. Notably, 25 peptic ulcer patients without T2DM were defined as completely recovered following treatment. In addition, the number of circulating EPCs as well as their colony forming ability was significantly reduced (P<0.05) in the peptic ulcer patients with T2DM following ulcer treatment, compared with the other groups. Circulating EPC counts were significantly increased in peptic ulcer patients without T2DM, as compared with the healthy controls. With regards to colony formation, peptic ulcer patients without T2DM did not exhibit improved colony formation ability. In conclusion, the number of circulating EPCs and their colony-forming ability was significantly reduced in peptic ulcer patients with T2DM following ulcer treatment when compared with the other groups. This suggests that the poor curative effect of peptic ulcer treatment in these patients is associated with impairment of EPCs.

Endothelial Progenitor Cells (EPC) Count by Multicolor Flow Cytometry in Healthy Individuals and Diabetes Mellitus (DM) Patients.

The present study aimed to determine circulating Endothelial Progenitor Cell (EPC) counts by multicolor flow cytometry in healthy individuals and diabetic subjects by means of forming an analysis procedure using a combination of monoclonal antibodies (moAbs), which would correctly detect the circulating EPC count. The circulating EPC count was detected in 40 healthy individuals (20 Female, 20 Male; age range: 26 - 50 years) and 30 Diabetes Mellitus (DM) patients (15 Female, 15 Male; age range: 42 - 55) by multicolor flow cytometry (FCM) in a single-tube panel consisting of 5 CD45/CD31/CD34/CD309/ SYTO® and 16 monoclonal antibodies. Circulating EPC count was 11.33 (7.89 - 15.25) cells/µL in the healthy control group and 4.80 (0.70 - 10.85) cells/µL in the DM group. EPC counts were significantly lower in DM cases that developed coronary artery disease (53.3%) as compared to those that did not (p < 0.001). In the present study, we describe a method that identifies circulating EPC counts by multicolor flow cytometry in a single tube and determines the circulating EPC count in healthy individuals. This is the first study conducted on EPC count in Turkish population. We think that the EPC count found in the present study will be a guide for future studies.

Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model.

OBJECT Coil embolization is a safe, efficient, and minimally invasive technique for the treatment of intracranial aneurysms. However, coil embolization is associated with a higher risk of recurrence than clip ligation. In this study, the authors explore a new approach through the promotion of endothelial progenitor cells (EPCs) to optimize endothelialization of the aneurysm neck and reduce the risk of recurrence. METHODS A coiled aneurysm model was created in 48 adult male Sprague-Dawley rats via microsurgery. Half of these animals were treated with rosuvastatin (20 mg/kg) in saline via gavage for 10, 20, or 30 days. The other half were administered saline without rosuvastatin. An additional 15 rats underwent "mock surgery" (identical anesthesia and saline gavage but no surgery). The endothelial repair process in the coiled aneurysms was evaluated via flow cytometry, im-munostaining, and electronic microscopy. The mock surgery group was used for comparison in flow cytometry studies. The effects of rosuvastatin on viability and functioning of Sprague-Dawley rat bone marrow-derived EPCs were also explored via MTT, migration, and tube formation assays. RESULTS The aneurysm neck repair score was significantly higher in the rosuvastatin-treated rats than in the untreated rats (p < 0.05). The circulating EPC count was increased and maintained at a higher level in rosuvastatin-treated rats compared with the aneurysm rats that did not receive rosuvastatin (p < 0.05). Immunostaining showed that the aneurysm neck endothelium was more integrated and the number of kinase insert domain receptor-positive cells was increased in the rosuvastatin-treated rats. Further study demonstrated that rosuvastatin promoted EPC proliferation, migration, and tube formation. CONCLUSIONS Rosuvastatin promoted endothelialization of the coiled aneurysm neck via induction of EPCs, suggesting that promoting endothelialization provides an additional therapeutic opportunity during vascular endothelium repair.

Exercise-induced mobilisation of endothelial progenitor cells in patients with premature coronary heart disease.

Endothelial progenitor cells (EPC) derive from bone marrow and participate in both endothelial regeneration and development of new blood vessels. EPC also play a role in the atherosclerotic process, and their number correlates negatively with the presence of classical risk factors. To evaluate circulating EPC count and their exercise-induced mobilisation in patients with premature coronary artery disease (CAD). The study group included 60 patients with stable CAD diagnosed before 45 years of age. The control group consisted of 33 healthy age- and gender-matched volunteers. Venous blood was sampled 3 times in order to assess circulating EPC count immediately before an exercise test (EPC 0) and at 15 min (EPC 15) and 60 min (EPC 60) after the exercise test. Circulating EPC count in the study group at rest and at 15 min after exercise was comparable (2.1 vs. 2.1 cell/μL, p = 0.35) and increased significantly at 60 min after exercise in comparison to resting values (2.1 vs. 3.2 cell/μL, p < 0.00001). In the control group, circulating EPC count increased significantly at 15 min after exercise (2.0 vs. 3.5 cell/μL, p < 0.0001) but later decreased at 60 min after exercise, although it remained greater than at rest (2.7 vs. 2.0 cell/μL, p < 0.0002). Circulating EPC count at rest and at 60 min after exercise was comparable in the two groups (2.1 vs. 2.0 cell/μL, p = 0.96; and 3.2 vs. 2.7 cell/μL, p = 0.13, respectively) but it was significantly lower in the study group compared to the control group at 15 min after exercise (2.1 vs. 3.5 cell/μL, p < 0.00001). Circulating EPC count at rest and at 15 min after exercise did not correlate with the number of stenosed coronary arteries but at 60 min after exercise it was greater in patients with one-vessel disease compared to those with two- or three-vessel disease (4.2 vs. 3.4 cell/μL, p = 0.01; and 4.2 vs. 2.3 cell/μL, p = 0.00003). However, no difference in circulating EPC count was seen at 60 min after exercise between patients with two- or three-vessel disease (3.4 vs. 2.3 cell/μL, p = 0.3). 1. Circulating EPC count at rest is comparable between subjects with premature atherosclerosis and healthy volunteers. 2. A single bout of physical exercise causes a significant increase in circulating EPC count in both groups, but the dynamics of exercise-induced EPC mobilisation is different, with delayed exercise-induced EPC mobilisation in subjects with premature CAD. 3. The extent of atherosclerotic coronary lesions does not influence circulating EPC count at rest.

Circulating Endothelial Progenitor Cell Levels Predict Cardiovascular Events in End-Stage Renal Disease Patients on Maintenance Hemodialysis

Background: The number of circulating endothelial progenitor cells (EPCs) has been identified as a surrogate biologic marker for vascular function and cumulative cardiovascular (CV) risk in the general population. Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have markedly decreased EPC counts and function. We hypothesized that the number of circulating EPCs predicts death from all causes and CV events in patients with ESRD on HD. Methods: We quantified the EPCs in blood samples from 70 patients with ESRD on HD. Circulating EPCs were counted by flow cytometry as the number of CD45^lowCD34⁺VEGFR2⁺ cells. Death from all causes and CV events served as outcome variables over a median follow-up period of 20 months. Results: It has been postulated that the number of circulating EPCs at baseline ranged from 1 to 350 cells/200 μl, with a mean of ± standard deviation (SD) of 26.0 ± 48.2 cells/200 μl. The median, lowest and highest tertiles of EPC counts were 11.0, 9.0, and 17.0 cells/200 μl, respectively. Patients with the lowest tertile EPC counts had significantly higher rates of CV events, but mortality was similar between the two groups. After adjusting for these risk factors, HbA1c and the lowest tertile EPC count remained as independent predictors of CV events. A cutoff value of 9.5 cells/200 μl maximized the power of the EPC count to predict future CV events as determined by ROC curve analysis. Conclusions: Reduced circulating EPC counts independently predicted CV events in 70 patients with ESRD on maintenance HD. Circulating EPCs may play a role in vascular repair, thereby affecting the clinical course of CV events.

Poor Outcome of Experimental Ischemic Stroke in Type 2 Diabetic Rats: Impaired Circulating Endothelial Progenitor Cells Mobilization

It is well accepted that type 2 diabetic mellitus (T2DM) results in the poor outcome of ischemic stroke. However, the mechanisms by which T2DM causes aggravated cerebral ischemic/reperfusion (I/R) injury are not clear. Recently, endothelial progenitor cells (EPCs) are considered to be related with the outcome of ischemic stroke. More importantly, T2DM can affect the function of circulating EPCs. This study tried to investigate whether T2DM worsens the cerebral I/R injury via affecting circulating EPCs. We used high-fat diet-fed and low-dose streptozotocin-treated male rats receiving middle cerebral artery occlusion surgery as animal model of focal cerebral I/R injury with T2DM (diabetic operated). And the rats were divided into 4 groups: normal sham, diabetic sham, normal operated, and diabetic operated. We measured the circulating EPCs counts and the levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in peripheral plasma of 4 groups. We found that diabetic rats subjected to I/R exhibited significantly severe deterioration in neurologic deficits compared with nondiabetic counterparts, which manifested higher infarct volume and cell apoptosis as well as lower neurologic defective score. There was no significant difference on the plasma glucose of groups before cerebral I/R injury compared with that of the groups posterior to cerebral I/R injury despite cerebral I/R injury had the tendency to increase the plasma glucose no matter in the presence or the absence of T2DM. In addition, there were the marked downregulation of circulating EPCs counts and the levels of VEGF and eNOS in diabetic rats before the cerebral I/R injury. Despite I/R injury without T2DM, there was a significant increase in the circulating EPCs counts, the circulating EPCs counts in I/R injury with T2DM group were significantly decreased compared with those in the other 3 groups. We also observed that the level of eNOS was significantly improved by I/R injury without considering the presence of T2DM. Thus, our present study suggested that it might be the impaired EPCs mobilization into theblood that contributed to the worse outcome of cerebral I/R injury with T2DM.

Correlation between the Reduced Circulating Endothelial Progenitor Cell Counts and Elevated Intraocular Pressure-Induced Retinal Ganglion Cell Apoptosis

ABSTRACTPurpose: To investigate the correlations between intraocular pressure (IOP) and circulating endothelial progenitor cells (EPCs), retinal ganglion cells (RGC) apoptosis and EPCs, and explore the possible role of EPCs in the elevated IOP-induced RGC apoptosis.Materials and methods: A rat model of IOP elevation was induced by photocoagulation of the limbus vein and episcleral veins using a 532-nm green laser. Twenty rats were randomly assigned to normal control (NC) group, 30 rats were randomly assigned to sham-treated control (STC) group and 50 rats were randomly assigned to laser-treated (LT) group. The IOPs were measured with a Tono-pen XL tonometer. Hematoxylin-eosin staining was performed to observe the effects of IOP elevation on the structure of retina. Retinal apoptotic cells were determined by in situ TUNEL staining, and peripheral blood EPCs (CD34+/CD133+) were detected by flow cytometry.Results: Compared with the NC group (9.9 ± 1.2 mmHg), the IOPs in the LT group were 37.4 ± 1.5, 31.8 ± 4.1, 25.9 ± 2.2, 23.1 ± 3.6 and 22.4 ± 3.0 mmHg on the third day, seventh day, third week, second month and third month, respectively, after the laser photocoagulation. There were significant differences in IOPs between the groups at the different time points (F = 110.02, p < 0.001). TUNEL analysis showed that only few apoptotic RGCs were found on the third and the seventh day after the laser treatment, and then many more apoptotic RGCs were found beginning on the third week after the laser treatment. The EPC counts were 121.3 ± 22.4, 81.3 ± 23.7, 46.1 ± 15.8, 54.4 ± 19.1 and 54.7 ± 15.9 /2 × 105 mononuclear cells (MNCs) on the third day, seventh day, third week, second month and third month, respectively, after the laser photocoagulation, compared with the NC group (62.1 ± 13.1)/2 × 105 MNCs. There were significant differences in EPC counts between the groups at the different time points (F = 22.09, p < 0.001).Conclusions: Elevated IOP-induced RGC apoptosis is associated with the reduced circulating EPC counts.

Circulating Endothelial Progenitor Cells as Markers for Severity of Ischemic Chronic Heart Failure

IntroductionDespite a high potential of endothelial progenitor cells (EPCs) for diagnostic purposes, the EPC role in developing ischemic chronic heart failure (CHF) has not been determined obviously.The objective of this study was to assess the counts of CD45+CD34+, CD45−CD34+, CD14+CD309+, and CD14+CD309+Tie2+ phenotyped circulating EPCs of various subpopulations in patients with ischemic CHF. Methods and ResultsThe study involved 153 patients (86 male), aged 48–62 years, with angiographically proven coronary artery disease (CAD) and 25 healthy volunteers. CHF was diagnosed in 109 patients (71.2%). Mononuclear cell populations were phenotyped by flow cytofluorimetry. Cardiovascular risk factors, such as type 2 diabetes mellitus, hyperlipidemia, arterial hypertension, and adherence to smoking, may have a negative effect on circulating EPC counts in CAD patients regardless of the presence of CHF. The depletion of the CD14+CD309+- and CD14+CD309+Tie2+-phenotyped circulating EPC counts is associated with the severity of left ventricular dysfunction, whereas the CD45+CD34+- and CD45−CD34+-mononuclear cell counts are more representative of the severity of atherosclerotic coronary artery lesions. ConclusionThe authors found that New York Heart Association functional class of CHF, left ventricular ejection fraction <42%, the N-terminal pro–B-type natriuretic peptide level >554 pg/mL, and Е/Еm ratio >15 U had the highest predictive value for the depletion of the EPC count in CAD patients.

Endothelial progenitor cells in acute ischemic stroke

ObjectivesThe levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points.Material and methodsWe studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0–2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry.ResultsWe included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes.ConclusionsAfter acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months.

Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes

BackgroundSuboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial. The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus (DM). MethodsIn a double-blind, placebo-controlled trial, we randomized 100 type 2 DM patients to vitamin D supplement (5000 IU/day, n = 50) or placebo (controls, n = 50) for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilatation (FMD), circulating levels of endothelial progenitor cells (EPCs) and brachial-ankle pulse wave velocity, and metabolic parameter, high-sensitivity C-reactive protein (hsCRP) and oxidative stress markers were performed before and after the supplementation. ResultsAfter 12 weeks, vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [25(OH)D] concentration (treatment effect 34.7 ng/mL, 95% CI 26.4–42.9, P < 0.001) and serum ionized calcium (treatment effect 0.037 mmol/L, 95% CI 0.007–0.067, P = 0.018); decreased serum parathyroid hormone concentration (treatment effect −0.55 pmol/L, 95% CI −1.08 to −0.02, P = 0.042) compared to patients who received placebo. Nevertheless, vitamin D supplementation did not improve vascular function as determined by FMD, circulating EPC count or baPWV (all P > 0.05). Furthermore, hsCRP, oxidative stress markers, low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups (all P > 0.05). ConclusionIn patients with type 2 DM, 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress. Clinical trial numberHKCTR-867, www.hkclinicaltrials.com.

Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells

Cranberry juice (CJ) contains a remarkably high concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 × 230 ml) over 4 months has beneficial effects on vascular function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular. A total of 84 participants (49.5 ± 16.2 years) with peripheral endothelial dysfunction and cardiovascular risk factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol-32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry. Baseline characteristics were similar in both groups. The effect of CJ on peripheral endothelial function and on circulating EPC counts (CD34(+)/CD133(+)/KDR(+)) did not change during the study. A high percentage of EPCs expressed osteocalcin (59.4 ± 35.7%). CJ, as compared to placebo, induced a decrease in the fraction of EPCs expressing osteocalcin (-8.64 ± 48.98 and 19.13 ± 46.11%, respectively, p = 0.019). Systemic levels of the adhesion marker ICAM correlated significantly with the number of EPCs expressing osteocalcin. The study demonstrated that long-term supplementation of polyphenol-rich CJ did not improve peripheral endothelial function. However, the decrease in the fraction of osteocalcin+ EPCs suggests a potential beneficial effect of polyphenol-rich CJ.

Impact of ADMA, endothelial progenitor cells and traditional cardiovascular risk factors on pulse wave velocity among prediabetic individuals

BackgroundCentral arterial stiffness represents a well-established predictor of cardiovascular disease. Decreased circulating endothelial progenitor cells (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional cardiovascular risk factors and insulin resistance have all been associated with increased arterial stiffness. The correlations of novel and traditional cardiovascular risk factors with central arterial stiffness in prediabetic individuals were investigated in the present study.MethodsThe study population consisted of 53 prediabetic individuals. Individuals were divided into groups of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking history, body mass index (BMI), waist to hip ratio (WHR), waist circumference (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or statin therapy were obtained from all participants. Insulin resistance was evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral pulse wave velocity was used as an index of arterial stiffness. Circulating EPC count and ADMA serum levels were also determined.ResultsAmong studied individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol, and ADMA levels positively correlated with pulse-wave velocity while exercise and GFR correlated negatively. EPC count did not correlate with PWV. In multivariate stepwise regression analysis PWV correlated independently and positively with LDL-Cholesterol (low density lipoprotein) and ADMA levels and negatively with exercise.ConclusionsElevated ADMA and LDL-C levels are strongly associated with increased arterial stiffness among pre-diabetic subjects. In contrast exercise inversely correlated with arterial stiffness.

The reliability of endothelial progenitor cells (CD34+, KDR+, and CD34+/KDR+) in the diagnosis of coronary artery disease and its severity

Background Bone marrow-derived endothelial progenitor cells (EPCs) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Changes in EPC number and function during coronary heart disease allow their use as a biomarker. However, so far, there is no suggested definite level at which we can diagnose coronary artery disease (CAD) or determine the severity of the disease. Aim of the work To assess the sensitivity, specificity, and accuracy of the circulating EPCs count to diagnose coronary heart disease and to predict the severity of the disease. Patients and methods The percentage and count of circulating EPCs (CD34+KDR+, CD34+, and KDR+) were measured by flow cytometry in 52 patients who underwent diagnostic angiography. The correlation between the level of the EPCs on the one hand and the presence or absence of CAD and the Gensini score calculated for each patient on the other was determined. Results Thirty-eight patients were found to have CAD and 14 had normal coronaries. For those with CAD, 22 had single-vessel disease and 16 had multiple vessel disease. It was found that EPCs (CD34+KDR+% and count and CD34+%) were significantly lower in patients with CAD compared with those with normal coronaries. CD34+KDR+% had an AUROC of 0.846 to diagnose CAD, with a sensitivity of 45.5%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 64.3%, and an accuracy of 72.75%. CD34+% and count and CD34+KDR+ count were negatively correlated with the Gensini score. CD34+% has an AUROC of 0.802 to diagnose the Gensini score of more than 6, with a sensitivity of 100%, a specificity of 55.2%, a PPV of 69%, an NPV of 100%, and an accuracy of 77.6%. Conclusion EPCs decrease in patients with CAD compared with those without CAD. CD34+KDR+% can diagnose CAD with a sensitivity, specificity, PPV, NPV, and accuracy of 45.55, 100, 100, 64.3, and 72.75%. CD34% can help to exclude the presence of severe CAD with a sensitivity, specificity, PPV, NPV, and accuracy of 100, 55.2, 69, 100, and 77.6%, respectively.

Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis

ObjectiveTo evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).MethodsCirculating endothelial progenitor cells (EPC), circulating endothelial cells and serum...

Effects of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes

Endothelial dysfunction is thought to be a critical event in the pathogenesis of vasculopathy in type 2 diabetes and oxidant stress is a major etiological factor. Gliclazide, a second generation sulfonylurea, contains an azabicyclo-octyl ring, which has been described to have antioxidant properties. However, the effect of gliclazide on endothelial function is unknown. Therefore, in this study, we examined the effect of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes (diabetic group; n = 33). A control group of non-diabetic subjects was also enrolled (n = 25). All of the diabetic patients were treated with gliclazide for 12 weeks. Endothelial function was evaluated by flow-mediated vasodilation (FMD) before and after treatment. We also determined the number of circulating endothelial progenitor cells (EPCs), which were defined by CD45 low/CD34 +/VEGFR2 + and quantified by flow cytometry, because these cells may offer a new biomarker for circulatory diseases. Oxidative stress was evaluated in terms of the serum levels of malondialdehyde, superoxide dismutase and nitric oxide. FMD, circulating EPC count and superoxide dismutase activity were significantly lower in the diabetic group than in the control group at baseline ( P < 0.05), and improved significantly following gliclazide treatment ( P < 0.05). Malondialdehyde and nitric oxide levels were higher in the diabetic group than in the control group at baseline ( P < 0.05), and decreased following gliclazide treatment. These results suggest that gliclazide could improve endothelial function in diabetes, which may be related to its antioxidant properties.

Exercise training increases endothelial progenitor cells and decreases asymmetric dimethylarginine in peripheral arterial disease: A randomized controlled trial

BackgroundSupervised exercise training (SET) is recommended as initial treatment to improve walking capacity in peripheral arterial disease (PAD) patients with intermittent claudication. Various mechanisms by which SET yields beneficial effects are postulated, however data regarding its influence on angiogenesis are scarce. Thus, we designed a prospective randomized controlled trial to study the impact of SET on markers of angiogenesis and endothelial function in PAD. MethodsForty PAD patients were randomized to SET on top of best medical treatment (SET+BMT) for 6 months versus best medical treatment (BMT) only. Endothelial progenitor cells (EPC) were assessed by whole-blood flow cytometry (co-expression of CD34+ CD133+ KDR+) and cell culture assays (endothelial cell-colony forming units, circulating angiogenic cells, migration assay) at baseline, 3, 6 and 12-months after inclusion. Changes of plasma levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and maximum walking distance were determined. ResultsEPC – measured by flow cytometric and cell culture techniques – increased significantly upon training paralleled by a significant decrease of ADMA when compared to the BMT group (p<0.05). Six months after training cessation, the beneficial effect of SET on EPC diminished, but maximum walking distance was significantly improved compared to baseline and controls (p<0.05). No significant changes were observed for VEGF and SDF-1 plasma levels in time course. ConclusionsSET increases circulating EPC counts and decreases ADMA levels reflecting enhanced angiogenesis and improved endothelial function, which might contribute to cardiovascular risk reduction.

Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy

The vascular endothelium is a critical determinant of diabetes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The mechanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The present review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.