Endothelial Progenitor Cells Biology Research Articles

Responses of Endothelial Progenitor Cells to Chronic and Acute Physical Activity in Healthy Individuals.

Endothelial progenitor cells (EPCs) are circulating cells of various origins that possess the capacity for renewing and regenerating the endothelial lining of blood vessels. During physical activity, in response to factors such as hypoxia, changes in osmotic pressure, and mechanical forces, endothelial cells undergo intense physiological stress that results in endothelial damage. Circulating EPCs participate in blood vessel repair and vascular healing mainly through paracrine signalling. Furthermore, physical activity may play an important role in mobilising this important cell population. In this narrative review, we summarise the current knowledge on the biology of EPCs, including their characteristics, assessment, and mobilisation in response to both chronic and acute physical activity in healthy individuals.

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.

Transplantation of endothelial progenitor cells overexpressing mir-126-3p improves vascular repair in a diabetic rat model.

Transplantation of endothelial progenitor cells overexpressing mir-126-3p improves vascular repair in a diabetic rat model.

The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair.

Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology.

Therapeutic Potential of Endothelial Progenitor Cells in Pulmonary Diseases.

Compromised alveolar development and pulmonary vascular remodeling are hallmarks of pediatric lung diseases such as bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Although advances in surfactant therapy, corticosteroids, and antiinflammatory drugs have improved clinical management of preterm infants, those who suffer with severe vascular complications still lack viable treatment options. Paucity of the alveolar capillary network in ACDMPV causes respiratory distress and leads to mortality in a vast majority of infants with ACDMPV. The discovery of endothelial progenitor cells (EPCs) in 1997 brought forth the paradigm of postnatal vasculogenesis and hope for promoting vascularization in fragile patient populations, such as those with BPD and ACDMPV. The identification of diverse EPC populations, both hematopoietic and nonhematopoietic in origin, provided a need to identify progenitor cell-selective markers that are linked to progenitor properties needed to develop cell-based therapies. Focusing on the future potential of EPCs for regenerative medicine, this review will discuss various aspects of EPC biology, beginning with the identification of hematopoietic, nonhematopoietic, and tissue-resident EPC populations. We will review knowledge related to cell surface markers, signature gene expression, and key transcriptional regulators and will explore the translational potential of EPCs for cell-based therapy for BPD and ACDMPV. The ability to produce pulmonary EPCs from patient-derived induced pluripotent stem cells invitro holds promise for restoring vascular growth and function in the lungs of patients with pediatric pulmonary disorders.

The State of Art of Regenerative Therapy in Cardiovascular Ischemic Disease: Biology, Signaling Pathways, and Epigenetics of Endothelial Progenitor Cells.

Ischemic heart disease is currently a major cause of mortality and morbidity worldwide. Nevertheless, the actual therapeutic scenario does not target myocardial cell regeneration and consequently, the progression toward the late stage of chronic heart failure is common. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that contribute to the homeostasis of the endothelial wall in acute and chronic ischemic disease. Calcium modulation and other molecular pathways (NOTCH, VEGFR, and CXCR4) contribute to EPC proliferation and differentiation. The present review provides a summary of EPC biology with a particular focus on the regulatory pathways of EPCs and describes promising applications for cardiovascular cell therapy.

Arrb2 promotes endothelial progenitor cell-mediated postischemic neovascularization.

Background and aim: Modulating biological functions of endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis in ischemic vascular diseases. This study aimed to explore the role and molecular mechanisms of β-arrestin 2 (Arrb2) in EPCs biology and angiogenic therapy.Methods: The influence of Arrb2 on postischemic neovascularization was evaluated in Arrb2-deficient mice. The proliferation, apoptosis, and various functions of EPCs were analyzed in vitro by manipulating the expression of Arrb2. Finally, the in vivo effect of Arrb2 on EPC-mediated neovascularization was investigated in a mouse model of hind-limb ischemia (HLI).Results: Arrb2-deficient mice exhibited impaired blood flow recovery based on laser Doppler measurements and reduced capillary density in the adductor muscle after unilateral HLI. Arrb2-deficient mice also showed restricted intraplug angiogenesis in subcutaneously implanted Matrigel plugs. In vitro, lentivirus-mediated Arrb2 overexpression promoted EPC proliferation, migration, adhesion, and tube formation, whereas Arrb2 knockdown had opposite effects. In addition, the overexpression of Arrb2 in EPCs protected them from hypoxia-induced apoptosis and improved intraplug angiogenesis ex vivo. Mechanistically, Arrb2 interacted with and activated extracellular signal-regulated kinase (ERK)1/2 and protein kinase B (Akt) signaling pathways. Finally, the transplantation of EPCs overexpressing Arrb2 resulted in a significantly higher blood flow restoration in ischemic hind limb and higher capillary density during histological analysis compared with control or Arrb2-knockdown EPC-treated nude mice.Conclusions: The data indicated that Arrb2 augmented EPC-mediated neovascularization through the activation of ERK and Akt signaling pathways. This novel biological function of Arrb2 might provide a potential therapeutic option to promote EPCs in the treatment of ischemic vascular diseases.

Augmented Survival, Angiogenic Properties and Mobilization of Human Endothelial Progenitor Cells Following Exposure to Sevoflurane

Anesthetic preconditioning (APC) with volatile agents has cardiac anti‐ischemic virtues that may be linked to stimulating effects of volatile anesthetics on stem cells biology. We investigated the influence of sevoflurane (Sevo) on apoptosis, proliferation, incorporation in tube‐like structure and mobilization of human endothelial progenitor cells (EPCs). 7‐days old cultured EPCs derived from human cord blood mononuclear cells were exposed in vitro to sevoflurane 2% or 4% in air/5% CO2, or only to air/5% CO2 (sham control) for 2 hrs in a modular chamber. Proliferation, apoptosis and incorporation of EPCs into tube‐like structures of HUVEC was evaluated 24 hrs later. EPCs plasma levels were evaluated by flow‐cytometry and in vitro culture assay before exposure to sevoflurane (1 MAC in 50% O2) or only to 50% O2 (sham control) and 24 hrs afterwards, in blood samples collected from coronary artery disease patients. Values are expressed as means ± SEM, compared by ANOVA. In the in vitro preconditioning setting, sevoflurane stimulated EPCs proliferation estimated by the MTS assay (n = 12, p < 0.01 for 2% Sevo, p < 0.001 for 4% Sevo) and by counting adherent DilAcLDL+/ FITC‐UEAI+ cells (n = 4, p < 0.01 for 2% Sevo, p < 0.001 for 4% Sevo), diminished apoptosis measured by annexin V/ propidium iodide assay (n = 5, p < 0.05 for both 2% and 4% Sevo), and raised the number of incorporated DiIAcLDL‐EPCs into HUVEC tube‐like structures (n = 4, p < 0.01 for 2% Sevo, p < 0.001 for 4% Sevo) when compared to control. Plasma CD45dim/CD34+/CD309+ and CD45dim/CD34+/CD309+/CD133+ mononuclear cell populations were increased in Sevo treated patients (n = 15) vs. the control group (n = 10) at 24 h post‐exposure vs. baseline (p < 0.01), and the number of adherent DilAcLDL+/FITC‐UEAI+ cells in 7 days old EPCs cultures was significantly higher in the study group vs. control between the same time points (p < 0.05). Our data prove that sevoflurane positively influences the biology of EPCs both in vivo and vitro, and may have an important cardioprotective impact in various interventional and surgical heart procedures by improving angiogenesis and ischemic tissue repair.Support or Funding InformationThe financial support was provided by UEFISCDI Romania, research grant PN‐II‐RUTE‐2012‐3‐0463.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Invited commentary

As the quest for stem cell-based therapies to treat nonhealing wounds continues, less effort has examined local, cutaneous treatments that may improve autogenous stem cell function. This exciting translational work by Dr Velazquez and colleagues examines local wound therapy using topical estrogen to improve stem cell function in diabetic wounds. This study is particularly important in light of recent clinical trials in which autogenous stem cells have been only modestly successful in improving healing in diabetic patients. It is likely that local therapy that improves the function of these cells will be necessary to see a significant difference in healing in the population of diabetic patients. This group attempts to tackle a challenging problem related to the impairment of stem cells in diabetic populations and to augment cell function by topical estrogen. In short, this study used a standard cutaneous wound model in a murine model of diabetes and treated mice with either topical estrogen or placebo for 5 days. The wounds were then harvested, and endothelial progenitor cells (EPCs) were examined for viability and proliferation as well as recruitment to the tissue. Mesenchymal stem cells (MSCs), which are well studied for their role in tissue regeneration, were examined at later time points for their role in repair and collagen deposition. They found that the wounds treated with estrogen had higher vessel density and increased EPC recruitment and the MSC activity was enhanced, resulting in increased scar density and collagen deposition. Perhaps most important, wound healing was significantly improved in the mice receiving estrogen. This is very exciting as this work holds a high potential for easy translation to human patients. Additional work will need to be done to ensure that there is minimal toxicity related to estrogen therapy applied locally. It is well known that repair of injury is dependent on progression through distinct overlapping phases; however, the failure of these phases to occur in timely progressive fashion will promote disease. In addition to therapies designed to target the EPCs and MSCs, it is likely that optimal therapy for diabetic wounds will include the targeting of other immune cell populations known to play a critical role in the tissue repair process. It is unknown whether topical estrogen therapy alters other immune cell populations involved in tissue repair. Furthermore, the mechanisms regarding how estrogen therapy is improving EPC and MSC function will need to be elucidated. Despite its minor limitations, this exciting translational study by the Velazquez laboratory is critical for advancing our knowledge of diabetic wound repair. The opinions or views expressed in this commentary are those of the author and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. The effect of estrogen on diabetic wound healing is mediated through increasing the function of various bone marrow-derived progenitor cellsJournal of Vascular SurgeryVol. 68Issue 6PreviewEndothelial progenitor cells (EPCs) are the key cells of postnatal neovascularization, and mesenchymal stem cells (MSCs) possess pluripotent differentiation capacity and contribute to tissue regeneration and wound healing. Both EPCs and MSCs are critical to the wound repair process, which is hindered in diabetes mellitus. Diabetes has been shown to decrease the function of these progenitor cells, whereas estrogen has beneficial wound healing effects. However, the role of estrogen in modulating EPC and MSC biology in diabetes is unknown. Full-Text PDF Open Access

Circulating Endothelial Progenitor Cells Biology and Regenerative Medicine in Pulmonary Vascular Diseases.

Pulmonary vascular disorders (PVDs) include primary or secondary diseases who ultimately influence the right heart function. Several researches showed that stem and progenitor cells may represent a novel approach in treating pulmonary hypertension. In particular, circulating endothelial progenitor cells (EPCs) are mobilized either from the bone marrow and/or arteries to replace dysfunctional endothelial cells and restore blood perfusion to ischemic tissues. They may deliver paracrine signals to stimulate local angiogenesis or may be physically incorporated within neovessels. Understanding the molecular mechanisms utilized by vascular endothelial growth factor (VEGF) to stimulate EPC might shed light on novel targets for regenerative medicine. Ca2+ machinery regulates proliferation, migration, tube formation, and, therefore, differentiation of EPCs may give valuable insights into the biology of these cells; the Ca2+ machinery in these cells is extremely plastic and may vary depending on their origin. In this paper, we review EPCs subtypes, their sources, biological properties, functional mechanisms and of course involvement in pulmonary vascular diseases.

Endothelial Progenitor Cells Biology in Diabetes Mellitus and Peripheral Arterial Disease and their Therapeutic Potential.

Endothelial progenitors are a population of cells with the inherent capacity to differentiate into mature endothelial cells and proangiogenic paracrine action. These characteristics have led to extensive studies being performed and tested in the treatment of tissue ischemia. The natural course of diabetes mellitus (DM) results in multiple areas of vascular damage. Thus endothelial progenitor cells'(EPCs) beneficial potential is particularly desirable in diabetic patients. In this review, we summarize contemporary knowledge of EPC biology in DM. It has been shown that EPC functions are considerably impaired by DM. The presence of peripheral arterial disease (PAD) seems to further exacerbate the deficiencies of EPCs. However, studies examining EPC counts in PAD and DM observed disparate results, which can be due to a lack of consensus on precise EPC immunotype used in the different studies. Nevertheless, the results of EPC-based autologous cell therapy (ACT) are promising. In addition, EPCs have been shown to bean independent predictor of cardiovascular risk and diabetic foot ulcer healing.

Circulating endothelial progenitor cells biology and regenerative medicine in pulmonary vascular diseases

Circulating endothelial progenitor cells biology and regenerative medicine in pulmonary vascular diseases

Transplantation of Endothelial Progenitor Cells Overexpressing miR-126-3p Improves Heart Function in Ischemic Cardiomyopathy.

In a previous study, a low level of miR-126-3p in endothelial progenitor cells (EPCs) was linked to the outcome of ischemic cardiomyopathy (ICM) patients. However, it remains unclear whether transplantation with miR-126-3p-overexpressing EPCs (MO-EPCs) can improve the cardiac function of ICM animal models. Methods and Results: miR-126-3p overexpression by lentiviral vector significantly increased migration and tube-like structures of EPCs from ICM patients. MO-EPCs or non-modified EPCs (NM-EPCs) were transplanted into nude rats with ICM induced by coronary artery ligation. MO-EPC transplantation increased capillary density and EPC survival rate in myocardial tissues of nude rats. Cytokines were also assessed by antibody array and real-time RT-PCR. G-CSF, VEGF-A, IL-3, IL-10, IGF-1, angiogenin, HGF, TIMP-1 and TIMP-2 were upregulated, and IL-8, MCP-1, MCP-2, TNF-α, TNF-β and MIP-1β were downregulated after miR-126-3p overexpression in EPCs. The same results were obtained in infarction tissues of nude rats after MO-EPC transplantation. Eight weeks after MO-EPC transplantation, left ventricular function improved significantly with clearly decreased infarction size, increased anterior wall thickness, and inhibition of inflammation compared with the results for NM-EPC transplantation. However, MO-EPC transplantation showed no increase in survival time of nude rats with ICM during 8 weeks of observation. miR-126-3p can restore the biology of EPCs from ICM patients. Moreover, MO-EPC transplantation improves cardiac function effectively, representing a promising future treatment for ICM.

Resveratrol protects late endothelial progenitor cells from TNF-α-induced inflammatory damage by upregulating Kr�ppel-like factor-2

Cardiovascular risk factors can negatively influence late endothelial progenitor cell (EPCs) number and functions, thus EPCs biology is a clinical implications for cardiovascular diseases. The present study aimed to investigate the potential protective effects of resveratrol (RES) on tumor necrosis factor (TNF)-α-induced inflammatory damage in late endothelial progenitor cells (EPCs) and to elucidate the underlying mechanisms. Late EPCs at passages 3–5 were pretreated with RES at a concentration of 20 µmol/l for 12 h and subsequently incubated with TNF-α (10 ng/ml) for 24 h. The adhesion, migration, proliferation and vasculogenesis of EPCs were subsequently detected. Furthermore, the mRNA expression levels of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Nitric oxide (NO) levels in the supernatant were determined using a colorimetric assay kit. Additionally, the mRNA and protein expression of Krüppel-like factor-2 (KLF2) was determined by RT-qPCR and western blot analysis, respectively. The results indicated that TNF-α markedly inhibited the proliferation, adhesion, migration and vasculogenesis of late EPCs. However, RES ameliorated the effects induced by TNF-α. Furthermore, exposure of EPCs to TNF-α decreased the levels of NO secretion and KLF2 expression at the mRNA and protein levels, but upregulated the levels of inflammatory factors, including ICAM-1 and MCP-1, compared with the control group. RES significantly inhibited TNF-α-induced inflammatory damage through upregulation of KLF2 expression and downregulation of the expression of ICAM-1 and MCP-1. In conclusion, RES may exert protective effects on the cardiovascular system, as demonstrated by the amelioration of TNF-α-induced inflammation in EPCs following RES treatment, and may therefore be used in the future for the prevention of cardiovascular disease.

Invited commentary

Invited commentary

Endothelial Progenitor Cell Biology and Vascular Recovery Following Transradial Cardiac Catheterization.

BackgroundTransradial catheterization is associated with radial artery injury and vasomotor dysfunction and represents an accessible model of acute vascular injury in humans. We characterized vascular injury and functional recovery to understand the role of circulating endothelial progenitor cells in vascular repair.Methods and ResultsIn 50 patients (aged 64±10 years, 70% male) undergoing transradial cardiac catheterization, radial artery injury was assessed by optical coherence tomography and examination of explanted vascular sheaths. Flow‐ and nitrate‐mediated dilatation of the radial artery was assessed in both arms at baseline, at 24 hours, and at 1, 4, and 12 weeks. Circulating endothelial progenitor cell populations were quantified using flow cytometry. Late endothelial outgrowth colonies were isolated and examined in vitro. Optical coherence tomography identified macroscopic injury in 12 of 50 patients (24%), but endothelial cells (1.9±1.2×104 cells) were isolated from all arterial sheaths examined. Compared with the noncatheterized radial artery, flow‐mediated vasodilatation was impaired in the catheterized artery at 24 hours (9.9±4.6% versus 4.1±3.1%, P<0.0001) and recovered by 12 weeks (8.1±4.9% versus 10.1±4.9%, P=0.09). Although the number of CD133+ cells increased 24 hours after catheterization (P=0.02), the numbers of CD34+ cells and endothelial outgrowth colonies were unchanged. Migration of endothelial cells derived from endothelial outgrowth colonies correlated with arterial function before catheterization but was not related to recovery of function following injury.ConclusionsTransradial cardiac catheterization causes endothelial denudation, vascular injury, and vasomotor dysfunction that recover over 12 weeks. Recovery of vascular function does not appear to be dependent on the mobilization or function of endothelial progenitor cells.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147119.

Therapeutic Potential of Endothelial Progenitor Cells in the Field of Orthopaedics.

Inadequate blood supply frequently impedes the viability of tissue-engineered constructs in the initial phase after implantation, and can lead to improper cell integration or cell death. Vascularization using stem cells has continued to evolve as a potential solution to this problem. In this review, we summarize studies that utilize endothelial progenitor cells (EPCs) for musculoskeletal regeneration. This review will also highlight recent concepts for EPC identification in conjunction with the development of EPC biology research. EPCs promote bone regeneration in animal models through a variety of mechanisms. By differentiating toward endothelial cell lineages and osteoblasts, EPCs stimulate vasculogenesis, angiogenesis and osteogenesis. Moreover, EPCs influence supporting cells through the secretion of growth factors and cytokines. Phase I/II clinical trials have applied circulating CD34+ cells/EPCs to nonunion bone fractures and have exhibited promising results including accelerated bone healing. Similar mechanisms of angiogenesis and osteogenesis are proposed for anterior cruciate ligament (ACL) ruptured tissue derived CD34+ cells, and thus EPCs have implied a critical role at the site of tendon-bone integration. EPCs are an emerging strategy among other cell-based therapies in the field of orthopaedics for the promotion of musculoskeletal regeneration.

Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer.

It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology. Instead, to promote angiogenesis cancer cell CCL5 may signal directly to endothelium in the tumor-stroma. In support of this hypothesis, we have also shown: (i) that endothelial cell CCR5 levels increases in response to tumor-conditioned media; (ii) that the amount of CCR5+ tumor vasculature correlates with invasive grade; and (iii) that inhibition of CCL5/CCR5 signaling impairs endothelial cell migration, associated with a decrease in activation of mTOR/AKT pathway members. Finally, we show that treatment with CCR5 antagonist results in less vasculature, impaired tumor growth, reduced metastases and improved survival. Taken as a whole, this work demonstrates that directly inhibiting CCR5 expressing vasculature constitutes a novel strategy for inhibiting angiogenesis and blocking metastatic progression in breast cancer.

Endothelial progenitor cells participation in cardiovascular and kidney diseases: a systematic review.

Endothelial progenitor cells (EPCs) represent a small population of blood cells (5-40 cells/mm(3)), with an ability to differentiate into endothelial cells that form the lining of the blood vessels and contribute to postnatal angiogenesis. Abundant evidence shows that recruitment of EPCs from the bone marrow, the monocyte/macrophage lineage and the organs facilitate the endothelial regeneration and repair. Changes in the number of EPCs were observed in both, chronic kidney and cardiovascular diseases. Thus, these cells were tested for usage in diagnosis and therapy. In this paper, we review the current knowledge on the EPC biology and contribution of these cells to the kidney and cardiovascular diseases.

Endothelial progenitor cell biology in psoriatic arthritis patients in the absence of traditional cardiovascular risk

IntroductionEndothelial progenitor cells (EPCs) restore dysfunctional endothelium and protect against atherosclerotic vascular disease. EPC population has been assessed in a heterogeneous population with equivocal results in psoriatic arthritis (PsA) patients with confounding factors. The aim of this study was to investigate EPC population in PsA patients in the absence of traditional cardiovascular risk factors. Methods22 active PsA patients and 20 age- and sex-matched healthy controls were included. EPCs (CD34+/CD133+) were assessed by Flow Cytometry. Endothelial function was assessed by measuring flow-mediated dilatation (FMD%) and carotid intima-media thickness (CIMT) was assessed by ultrasonography. Inflammatory markers, i.e. erythrocyte sedimentation rate, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1, were also assessed in all subjects. ResultsEPC population was significantly lower in PsA patients compared with controls (mean 0.028% vs. 0.047%, p<0.001). FMD and inflammatory markers were also significantly (p<0.05) altered as compared to healthy controls, but there was no significant difference in CIMT (mean 0.65 vs. 0.56, p=0.068). Specifically, CD34+CD133+cells correlated positively with FMD (r=0.66, p=0.002) and inversely correlated with CRP (r=−0.65, p=0.002), TNF-α (r=−0.58, p=0.01), IL-6 (r=−0.64, p=0.003), disease activity measures (DAS-28 (r=−0.63, p=0.004), and disease activity index for PsA (r=−0.53, p=0.02)). ConclusionsEPC population is depleted in PsA patients in the absence of traditional cardiovascular risk. Inflammation appears to play a key role in EPC depletion and the latter contributes to endothelial dysfunction in PsA.