Endothelial Progenitor Cells Levels Research Articles

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

Periodontal inflammation is associated with increased circulating levels of endothelial progenitor cells: a retrospective cohort study in a high vascular risk population.

One of the main biological mechanisms behind the link between periodontitis and atherosclerotic vascular diseases is vascular endothelial dysfunction. Particularly, circulating endothelial progenitor cells (EPCs) have been considered a biomarker of altered vascular endothelial function. The aim of this study was to investigate relationship between periodontal inflammation and increased number of circulating EPCs. This is retrospective cohort study. In this study, 85 elderly patients with a previous history of hypertension were followed up to 12 months. A baseline full-mouth periodontal assessment was carried out, and the amount of periodontal tissue inflamed per subject was calculated as a proxy of periodontal inflammation [periodontal inflamed surface area (PISA)]. The number of circulating EPCs (CD34+/CD133+/KDR+) was determined by flow cytometry from peripheral blood samples collected at baseline and 12 months. Mean concentrations of CD34+/CD133+/KDR+ progenitor cells were higher in periodontitis patients than in those without periodontitis at baseline [55.4, 95% confidence interval (CI) = 20.8 to 90.0 versus 27.2, 95% CI = 13.6 to 40.8, p = 0.008] and 12 months (114.6, 95% CI = 53.5 to 175.7 versus 19.1, 95% CI = 10.8 to 27.4, p = 0.003). A significant increase over the follow-up was noticed in the group of subjects with periodontitis (p = 0.049) but not in the nonperiodontitis group (p = 0.819). PISA was independently associated with CD34+/CD133+/KDR+ EPCs at baseline (B coefficient = 0.031, 95% CI = 0.005 to 0.058; p = 0.021). The relationship between PISA and CD34+/CD133+/KDR+ EPCs at 12 months was confounded by increased baseline body mass index (B coefficient = 0.064, 95% CI = -0.005 to 0.132; p = 0.066). Periodontal inflammation is associated with high number of CD34+/CD133+/KDR+ EPCs, thus supporting a potential link between periodontitis and endothelial dysfunction.

Endothelial progenitor cells and major adverse cardiovascular events in patients receiving elective coronary angiography

Background and purpose: The association of circulating endothelial progenitor cells (EPCs) with different cardiovascular diseases and their related major adverse cardiovascular events (MACE) remained inconclusive. We aimed to clarify associations between the circulating EPC levels and the risk of MACE concerning different atherosclerosis-related diseases. Methods: This prospective cohort study was conducted from December 2009 to March 2015. Patients who underwent non-emergent coronary angiography (CAG) were included. The circulating EPC levels were measured using flow cytometry prior to the CAG procedure. The study evaluation of circulating EPC levels among patients with obstructive coronary artery disease (CAD) and other comorbidities. Patients were then assigned to tertiles by circulating EPC levels to evaluate the predictive values of the development of MACEs. Results: The study enrolled 1099 patients, of whom, 736 (67%) were men, with a mean age of 66.7 ± 12.5 years old. Overall, 637 (58%) patients were diagnosed with obstructive CAD according to CAG. MACE occurred in 268 (24.4%) patients. Circulating EPC levels were lower in patients with peripheral artery disease (PAD) but not associated with the presence of obstructive CAD, atrial fibrillation, chronic kidney disease (CKD), heart failure, and diabetes mellitus. Higher circulating EPC levels are linked with higher MACE among patients with suspected CAD, regardless of the presence or absence of obstructive CAD or CKD. The association did not present in patients with PAD. Conclusions: Higher circulating EPC levels are associated with a greater risk of MACE, regardless of the presence of obstructive CAD or CKD. This association was not apparent in the patients with PAD, suggesting impaired endothelial repair in these patients.

Endothelial Progenitor Cells in Neurovascular Disorders—A Comprehensive Overview of the Current State of Knowledge

Endothelial progenitor cells (EPCs) are a population of cells that circulate in the blood looking for areas of endothelial or vascular injury in order to repair them. Endothelial dysfunction is an important component of disorders with neurovascular involvement. Thus, the subject of involvement of EPCs in such conditions has been gaining increasing scientific interest in recent years. Overall, decreased levels of EPCs are associated with worse disease outcome. Moreover, their functionalities appear to decline with severity of disease. These findings inspired the application of EPCs as therapeutic targets and agents. So far, EPCs appear safe and promising based on the results of pre-clinical studies conducted on their use in the treatment of Alzheimer’s disease and ischemic stroke. In the case of the latter, human clinical trials have recently started to be performed in this subject and provided optimistic results thus far. Whereas in the case of migraine, existing findings pave the way for testing EPCs in in vitro studies. This review aims to thoroughly summarize current knowledge on the role EPCs in four disorders with neurovascular involvement, which are Alzheimer’s disease, cerebral small vessel disease, ischemic stroke and migraine, with a particular focus on the potential practical use of these cells as a treatment remedy.

A Meta-Analysis of the Effects of Aerobic Exercise on the Basal Level of Endothelial Progenitor Cells in Middle-Aged and Older Adults.

Circulatory endothelial progenitor cells (EPCs) play an important role in repairing damaged vascular endothelium and preventing cardiovascular diseases. The decrease in level of circulating EPCs in middle-aged and older adults can lead to an increase in cardiovascular events. Researchers have carried out several studies on the effects of aerobic exercise on circulating EPCs in middle-aged and older adults, but the results vary from one study to another. The aim of this study therefore is to systematically evaluate the effect of aerobic exercise on the basal level of circulating EPCs in middle-aged and older adults by meta-analysis. Randomized controlled trial studies on the effects of aerobic exercise on EPCs were searched for from CNKI, PubMed, EBSCO, Cochrane Library, Web of Science, and Embase databases. The literature was screened according to inclusion and exclusion criteria, research data were extracted, and the literature quality was evaluated by Cochrane scale. Software Review Manager (version 5.3) and Stata (version 15.0) were used for data analysis. A total of nine articles were included in this analysis, including 165 participants (40 healthy adults and 125 patients) who received exercise interventions and 162 participants (40 healthy adults and 122 patients) who served as the control, with an age range from 58 to 70years. The meta-analysis found that long-term (≥12weeks) aerobic exercise could improve the level of EPCs in the peripheral circulation (standardized mean differences [SMD] = 0.53, 95% confidence interval [0.30, 0.76], p < .01). The subgroup analysis found that aerobic exercise improved EPCs in healthy people better than in people with cardiovascular disease and that the intervention time needs to be over 12weeks to have a significant impact. In conclusion, the authors suggest that middle-aged and older adults can improve their EPCs quantity by engaging in moderate-intensity aerobic exercise four to five times per week for no less than 12weeks to reduce the risk of cardiovascular disease.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Exercise Training Effects on Circulating Endothelial and Progenitor Cells in Heart Failure

Heart failure (HF) is a major public health issue worldwide with increased prevalence and a high number of hospitalizations. Patients with chronic HF and either reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) present vascular endothelial dysfunction and significantly decreased circulating levels of endothelial progenitor cells (EPCs). EPCs are bone marrow-derived cells involved in endothelium regeneration, homeostasis, and neovascularization. One of the unsolved issues in the field of EPCs is the lack of an established method of identification. The most widely approved method is the use of monoclonal antibodies and fluorescence-activated cell sorting (FACS) analysis via flow cytometry. The most frequently used markers are CD34, VEGFR-2, CD45, CD31, CD144, and CD146. Exercise training has demonstrated beneficial effects on EPCs by increasing their number in peripheral circulation and improving their functional capacities in patients with HFrEF or HFmrEF. There are two potential mechanisms of EPCs mobilization: shear stress and the hypoxic/ischemic stimulus. The combination of both leads to the release of EPCs in circulation promoting their repairment properties on the vascular endothelium barrier. EPCs are important therapeutic targets and one of the most promising fields in heart failure and, therefore, individualized exercise training programs should be developed in rehabilitation centers.

Glycaemic Control Achieves Sustained Increases of Circulating Endothelial Progenitor Cells in Patients Hospitalized for Decompensated Diabetes: An Observational Study.

Background and AimDiabetes reduces the levels of circulating endothelial progenitor cells (EPCs), which contribute to vascular homeostasis. In turn, low EPCs levels predict progression of chronic complications. Several studies have shown that hyperglycaemia exerts detrimental effects on EPCs. Improvement in glucose control with glucose-lowering medications is associated with an increase of EPCs, but only after a long time of good glycaemic control. In the present study, we examined the effect of a rapid glycaemic amelioration on EPC levels in subjects hospitalized for decompensated diabetes.MethodsWe used flow cytometry to quantify EPCs (CD34+/CD133+KDR+) in patients hospitalized for/with decompensated diabetes at admission, at discharge, and 2 months after the discharge. During hospitalization, all patients received intensive insulin therapy.ResultsThirty-nine patients with type 1 or type 2 diabetes were enrolled. Average (± SEM) fasting glucose decreased from 409.2 ± 25.9 mg/dl at admission to 190.4 ± 12.0 mg/dl at discharge and to 169.0 ± 10.3 at 2 months (both p < 0.001). EPCs (per million blood cells) significantly increased from hospital admission (13.1 ± 1.4) to discharge (16.4 ± 1.1; p = 0.022) and remained stable after 2 months (15.5 ± 1.7; p = 0.023 versus baseline). EPCs increased significantly more in participants with newly-diagnosed diabetes than in those with pre-existing diabetes. The increase in EPCs was significant in type 1 but not in type 2 diabetes and in those without chronic complications.ConclusionIn individuals hospitalized for decompensated diabetes, insulin therapy rapidly increases EPC levels for up to 2 months. EPC defect, reflecting impaired vascular repair capacity, may be reversible in the early diabetes stages.

N‑acetyl cysteine prevents ambient fine particulate matter‑potentiated atherosclerosis via inhibition of reactive oxygen species‑induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell.

Ambient fine particulate matter (PM) serves an important role in the development of cardiovascular disease, including atherosclerosis. Antioxidant N-acetyl cysteine (NAC) has protective effects in the cardiovascular system. However, it is unknown if NAC prevents PM-potentiated atherosclerosis in hyperlipidemia. Low-density lipoprotein (LDL) receptor knockout mice were pretreated with 1 mg/ml NAC in drinking water for 1 week and continued to receive NAC, high-fat diet and intranasal instillation of PM for 1 week or 6 months. Blood plasma was collected for lipid profile, oxidized (ox-)LDL, blood reactive oxygen species (ROS) and inflammatory cytokine (TNF-α, IL-1β and IL-6) measurement. Blood cells were harvested for endothelial progenitor cell (EPC) population and intracellular ROS analysis. Murine aorta was isolated for atherosclerotic plaque ratio calculation. NAC treatment maintained circulating EPC level and significantly decreased blood ox-LDL and ROS, inflammatory cytokines, mononuclear and EPC intracellular ROS levels as well as aortic plaque ratio. NAC prevented PM-potentiated atherosclerosis by inhibiting plasma ROS-induced ox-LDL elevation, mononuclear cell and EPC intracellular ROS-induced circulating EPC reduction and inflammatory cytokine production.

Change in Circulating Levels of Endothelial Progenitor Cells and Sexual Function in Women With Type 1 Diabetes.

ContextEndothelial progenitor cells (EPCs), which are involved in the mechanisms of vascular repair and sexual function, are decreased in diabetic women compared with general population.ObjectiveThis work aimed to investigate the circulating levels of EPCs and the change in sexual function during the menstrual cycle in women with type 1 diabetes (T1DM) compared with healthy women.MethodsThis case-control observational study was conducted at the Unit of Endocrinology and Metabolic Diseases at University Hospital “Luigi Vanvitelli’’ of Naples. Participants included 36 women with T1DM and 64 age-matched healthy controls. EPCs were quantified by flow cytometry and sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale. All assessments were made at the follicular, ovulatory, and luteal phases of the same menstrual cycle. Main outcome measures included differences in EPCs levels and sexual function between patients and controls.ResultsCompared with controls, women with T1DM showed significantly lower levels of both CD34 + (P < .001) and CD34 + CD133 + cells (P < .001) in the ovulatory phase, and CD34 + KDR + cells both in the ovulatory phase and in the luteal phase (P < .001 for both). Diabetic women showed significantly lower total FSFI scores and higher FSDS score than control women in all phases of the menstrual cycle. FSFI total score was predicted by both CD34 + CD133 + and CD34 + KDR + cells in the follicular phase, CD34 + and CD34 + KDR + CD133 + cells in the ovulatory phase, and CD34 + KDR + and CD34 + KDR + CD133 + cells in the luteal phase.ConclusionWomen with T1DM show lower levels of EPCs during the menstrual cycle compared with controls. EPCs count predicts sexual function in this selected population.

Endothelial Progenitor Cells as Biomarkers of Cardiovascular Pathologies: A Narrative Review.

Endothelial progenitor cells (EPC) may influence the integrity and stability of the vascular endothelium. The association of an altered total EPC number and function with cardiovascular diseases (CVD) and risk factors (CVF) was discussed; however, their role and applicability as biomarkers for clinical purposes have not yet been defined. Endothelial dysfunction is one of the key mechanisms in CVD. The assessment of endothelial dysfunction in vivo remains a major challenge, especially for a clinical evaluation of the need for therapeutic interventions or for primary prevention of CVD. One of the main challenges is the heterogeneity of this particular cell population. Endothelial cells (EC) can become senescent, and the majority of circulating endothelial cells (CEC) show evidence of apoptosis or necrosis. There are a few viable CECs that have properties similar to those of an endothelial progenitor cell. To use EPC levels as a biomarker for vascular function and cumulative cardiovascular risk, a correct definition of their phenotype, as well as an update on the clinical application and practicability of current isolation methods, are an urgent priority.

Circulating levels of endothelial progenitor cells (EPCs) and sexual function in fertile women with type 1 diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Far-Infrared Therapy Decreases Orthotopic Allograft Transplantation Vasculopathy.

Orthotopic allograft transplantation (OAT) is a major strategy for solid heart and kidney failure. However, the recipient’s immunity-induced chronic rejection induces OAT vasculopathy that results in donor organ failure. With the exception of immunosuppressive agents, there are currently no specific means to inhibit the occurrence of OAT vasculopathy. On the other hand, far-infrared (FIR) therapy uses low-power electromagnetic waves given by FIR, with a wavelength of 3–25 μm, to improve human physiological functions. Previous studies have shown that FIR therapy can effectively inhibit inflammation. It has also been widely used in adjuvant therapy for various clinical diseases, especially cardiovascular diseases, in recent years. Thus, we used this study to explore the feasibility of FIR in preventing OAT vasculopathy. In this study, the model of transplantation of an aorta graft from PVG/Seac rat to ACI/NKyo rat, and in vitro model of human endothelial progenitor cells (EPCs) was used. In this report, we presented that FIR therapy decreased the serious of vasculopathy in OAT-recipient ACI/NKyo rats via inhibiting proliferation of smooth muscle cells, accumulation of collagen, and infiltration of fibroblast in the vessel wall; humoral and cell-mediated immune responses were decreased in the spleen. The production of inflammatory proteins/cytokines also decreased in the plasma. Additionally, FIR therapy presented higher mobilization and circulating EPC levels associated with vessel repair in OAT-recipient ACI/NKyo rats. In vitro studies demonstrated that the underlying mechanisms of FIR therapy inhibiting OAT vasculopathy may be associated with the inhibition of the Smad2-Slug axis endothelial mesenchymal transition (EndoMT). Thus, FIR therapy may be the strategy to prevent chronic rejection-induced vasculopathy.

Endothelial Progenitor Cell Response to Acute Multicomponent Exercise Sessions with Different Durations.

Simple SummaryReports suggest that an acute bout of exercise promotes the mobilization of endothelial progenitor cells from bone marrow, increasing the circulating levels of endothelial progenitor cells. The impact of the intensity of acute exercise on the circulating levels of endothelial progenitor cells was previously described. Yet, the question of whether the duration of the exercise session impacts the mobilization of endothelial progenitor cells has not been tested among adults with cardiovascular risk factors. In this study, a 30 min session vs. a 45 min session promoted a significant increase in the circulating number of endothelial progenitor cells. The findings show a multicomponent exercise session of only 30 min has the potential to induce beneficial effects for vascular health. It is widely accepted that exercise training has beneficial effects on vascular health. Although a dose-dependent relation has been suggested, little is known about the effects of different exercise durations on endothelial markers. This study aimed to assess the effect of single exercise sessions with different durations in the circulating levels of endothelial progenitor cells (EPCs) and endothelial cells (CECs) among adults with cardiovascular risk factors. Ten participants performed two multicomponent exercise sessions, one week apart, lasting 30 and 45 min (main exercise phase). Before and after each exercise session, blood samples were collected to quantify EPCs and CECs by flow cytometry. The change in EPCs was significantly different between sessions by 3.0% (95% CI: 1.3 to 4.7), being increased by 1.8 ± 1.7% (p = 0.009) in the 30 min session vs. −1.2 ± 2.0% (p > 0.05) in the 45 min session. No significant change was observed in CECs [−2.0%, 95%CI: (−4.1 to 0.2)] between the sessions. In conclusion, a multicomponent exercise session of 30 min promotes an acute increase in the circulating levels of EPCs without increasing endothelial damage (measured by the levels of CECs) among adults with cardiovascular risk factors.

Endothelial function and endothelial progenitor cells in systemic lupus erythematosus

The observations that traditional cardiovascular disease (CVD) risk factors fail to fully account for the excessive cardiovascular mortality in patients with systemic lupus erythematosus (SLE) compared with the general population have prompted in-depth investigations of non-traditional, SLE-related risk factors that contribute to cardiovascular complications in patients with SLE. Of the various perturbations of vascular physiology, endothelial dysfunction, which is believed to occur in the earliest step of atherosclerosis, has been extensively investigated for its contribution to CVD risk in SLE. Endothelial progenitor cells (EPCs), which play a crucial part in vascular repair, neovascularization and maintenance of endothelial function, are quantitatively and functionally reduced in patients with SLE. Yet, the lack of a unified definition of EPCs, standardization of the quantity and functional assessment of EPCs as well as endothelial function measurement pose challenges to the translation of endothelial function measurements and EPC levels into prognostic markers for CVD in patients with SLE. This Review discusses factors that contribute to CVD in SLE, with particular focus on how endothelial function and EPCs are evaluated currently, and how EPCs are quantitatively and functionally altered in patients with SLE. Potential strategies for the use of endothelial function measurements and EPC quantification as prognostic markers of CVD in patients with SLE, and the limitations of their prognostication potential, are also discussed.

Endothelial Progenitor Cells in Coronary Artery Disease: From Bench to Bedside.

Endothelial progenitor cells (EPCs) are a heterogeneous group of cells present in peripheral blood at various stages of endothelial differentiation. EPCs have been extensively investigated in patients with coronary artery disease (CAD), with controversial findings both on their role in atherosclerosis progression and in the process of neointimal growth after a percutaneous coronary intervention (PCI). Despite nearly 2 decades of experimental and clinical investigations, however, the significance of EPCs in clinical practice remains unclear and poorly understood. This review provides an update on the role of EPCs in the most common clinical scenarios that are experienced by cardiologists managing patients with CAD. We here summarize the main findings on the association of EPCs with cardiovascular risk factors, coronary atherosclerosis, and myocardial ischemia. We then discuss the potential effects of EPCs in post-PCI in-stent restenosis, as well as most recent findings with EPC-coated stents. Based on the mounting evidence of the relationship between levels of EPCs and several different adverse cardiovascular events, EPCs are emerging as novel predictive biomarkers of long-term outcomes in patients with CAD.

Osteogenic Circulating Endothelial Progenitor Cells are Associated with Vascular Aging of the Large Arteries in Rheumatoid Arthritis

Background and AimRheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis.MethodsWe performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography.ResultsOsteogenic EPCs OCN+CD34+KDR+ (P = 0.002) and OCN+CD34+ (P = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all P < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], P = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], P < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], P = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI −0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively).ConclusionCirculating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.

Reduced Levels of Circulating Endothelial Cells and Endothelial Progenitor Cells in Patients with Heart Failure with Reduced Ejection Fraction

Endothelial dysfunction has been suggested as a potential mechanism contributing to the development and progression of heart failure (HF). Levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), and hematopoietic stem and progenitor cells (HSPCs) have been recognized as useful markers of vascular damage and endothelial repair in response to tissue injury. To evaluate the circulating levels of EPCs, CECs, and HSPCs among patients with HF with reduced ejection fraction (HFrEF). In 82 individuals (42 patients with HFrEF and 42 age-matched subjects without established cardiovascular disease), peripheral blood was drawn and levels of EPCs, CECs, and HSPCs were quantified by flow cytometry. Patients with HFrEF showed lower levels of circulating EPCs (5.28×10-3 ± 6.83×10-4% vs. 7.76×10-3 ± 4.91×10-4%, p ≤0.001) and CECs (5.11×10-3 ± 7.87×10-4% vs. 6.51×10-3 ± 5.21×10-4%, p=0.005) when compared to the age-matched group. Circulating levels of HSPCs were not significantly different between groups (p=0.590). Additionally, the number of EPCs and CECs was significantly higher in HFrEF patients with overweight/obesity (n=24) compared to patients with normal weight (n=17). Circulating levels of EPCs and CECs were significantly decreased in patients with HFrEF in comparison to age-matched subjects without established cardiovascular disease, suggesting that the levels of CECs and EPCs may be potential biomarkers of the cellular response to vascular injury in patients with HFrEF.

Endothelial Progenitor Cell Levels and Extent of Post-prandial Lipemic Response.

Background and ObjectiveDue to the frequency of meal ingestion, individuals spend the majority of the day, ~18 h, in a status of post-prandial (PP) stress. Remnant-like lipoprotein particles (RLPs) are predominant in PP phase playing an important role in the development of atherosclerosis. Endothelial progenitor cells (EPCs) have been suggested to play a role in vessel wall homeostasis and in reducing atherosclerosis. However, there is no information about peripheral blood EPCs number following PP stress. We investigated the association between circulating EPCs levels and extent of PP lipemia in healthy subjects following a high-fat meal.Materials and MethodsA total of 84 healthy subjects (42 men, 42 women) aged 17–55 years were included in the study. PP lipemic response of subjects was determined by Oral Fat-Loading Test (OFLT). All the subjects were classified on the basis of their plasma TG levels after PP lipemic stressors in categories 1 (low), 2 (moderate), and 3 (high). Circulating EPCs numbers were measured by the flow cytometry method.ResultsThere was a significant difference in terms of lipid parameters between men and women: high-density lipoprotein cholesterol (HDL-C) was significantly lower in men than in women (p < 0.001). Total cholesterol (TC) (p = 0.004), low-density lipoprotein cholesterol (LDL-C) (p < 0.001), triglyceride (TG) (p < 0.001), and TG-AUC (p < 0.001) were significantly higher in men than in women. There was no significant difference between the genders in terms of CD34+KDR+ and CD34+KDR+CD133+cell number and MMP-9 levels. Vascular endothelial growth factor (VEGF) levels were significantly higher in men than women (p = 0.004). TC, LDL-C, and TG were significantly higher in the 3rd category than 1st and 2nd categories (p < 0.001) in women. Age, body mass index (BMI), fat rate, TG, TC, and LDL-C were significantly higher in the 3rd category than 1st category (p < 0.001, p = 0.002, p = 0.002, p = 0.01, p = 0.007, p = 0.004; respectively), in men. Circulating numbers of EPCs in men were significantly higher in the PP hyperlipidemia group than in the low TG levels category, independently from age (p < 0.05). Circulating EPC levels showed a positive correlation with OFLT response in men (r = 0.414, p < 0.05). Also, OFLT response showed a strong positive correlation with fasting TG levels (r = 0.930, p < 0.001). EPC levels in categories of women were not different.ConclusionIncreased EPCs levels in subjects with different PP hyperlipidemia may be associated with a response to endothelial injury, related to increased atherogenic remnant particles at the PP phase.

Tempol Preserves Endothelial Progenitor Cells in Male Mice with Ambient Fine Particulate Matter Exposure.

Ambient fine particulate matter (PM) exposure associates with an increased risk of cardiovascular diseases (CVDs). Major sex differences between males and females exist in epidemiology, pathophysiology, and outcome of CVDs. Endothelial progenitor cells (EPCs) play a vital role in the development and progression of CVDs. PM exposure-induced reduction of EPCs is observed in male, not female, mice with increased reactive oxygen species (ROS) production and oxidative stress. The lung is considered an important source of ROS in mice with PM exposure. The aim of the present study was to investigate the sex differences in pulmonary superoxide dismutase (SOD) expression and ROS production, and to test the effect of SOD mimic Tempol on the populations of EPCs in mice with PM exposure. Both male and female C57BL/6 mice (8–10 weeks) were exposed to intranasal PM or vehicle for 6 weeks. Flow cytometry analysis demonstrated that PM exposure significantly decreased the levels of EPCs (CD34+/CD133+) in both blood and bone marrow with increased ROS production in males, but not in females. ELISA analysis showed higher levels of serum IL-6 and IL-1βin males than in females. Pulmonary expression of the antioxidant enzyme SOD1 was significantly decreased in males after PM exposure, but not in females. Administration of the SOD mimic Tempol in male mice with PM exposure attenuated the production of ROS and inflammatory cytokines, and preserved EPC levels. These data indicated that PM exposure-induced reduction of EPC population in male mice may be due to decreased expression of pulmonary SOD1 in male mice.