Decrease In Endothelial Progenitor Cells Research Articles

Abstract 111: Elevated Sympathetic Drive to the Bone Marrow Contributes to the Inflammatory Response and Dysfunctional Endothelial Progenitor Cells in the Spontaneously Hypertensive Rat

Introduction: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) contribute to the repair of vasculature, whereas the inflammatory cells (ICs) contribute to the vascular damage. Thus, imbalanced EPC/IC ratio, coupled with dysfunctional EPCs, are key in the vascular pathophysiology of hypertension. We demonstrated that SHR, which have elevated sympathetic drive, exhibit a significantly lower BM EPC/IC ratio due to lower EPCs and higher ICs. The inverse relationship between the sympathetic drive and EPC/IC ratio is supported by our data showing that elevation in the overall sympathetic drive in the WKY, as a result of the light:dark cycle, decreases the EPC/IC ratio. This has led us to propose that the SHR exhibit chronically elevated sympathetic drive to the BM, which contributes to the impaired EPC/IC ratio and EPC dysfunction. Methods: Femur from 21-week old SHRs (MAP=∼145 mmHg) and WKYs (MAP=∼100 mmHg) were used to determine norepinephrine (NE) and tyrosine hydroxylase (TH) levels. Femur BMs were flushed, and cell supernatants collected for NE measurements (ELISA). Femurs from a separate group of rats were fixed and used for TH quantification (IHC). Additional WKY and SHR were used for BM injection of GFP-tagged pseudorabies virus (GFP-PRV) to compare the extent of retrograde labeling from the femur BM to the brain autonomic areas (SFO, PVN, RVLM, NTS). Results: We observed a ∼80% higher NE levels, and a ∼2.1 fold higher TH density, in the BM of SHR compared to WKY. This was accompanied by a ∼52% decrease in EPC/IC ratio and a ∼44% decrease in EPC function in the SHR compared to the WKY. Additional evidence for the increased sympathetic communication between the SHR autonomic brain areas and the BM was provided by PRV-GFP retrotracing. The data showed a profound labeling of the PVN neurons in the SHR compared to WKY, 7 days post-PRV-GFP injection. Less significant labeling was observed in other autonomic areas (RVLM>NTS>SFO) under similar conditions. Conclusion: These observations demonstrate, for the first time, that there is an elevated sympathetic drive to the BM in the SHR. This is associated with an impaired BM activity, reflecting a decrease in EPCs and increase in ICs, which may contribute to the vascular pathophysiology in neurogenic hypertension.

Change of vascular endothelial progenitor cell in acute angle-closure glaucomatous patient

Background The circulating endothelial progenitor cells (EPCs)play an important role in postnatal vasculogenesis and restoration of endothelial injury.Previous investigation illustrated that a reduced ocular blood flow and vascular dysfunction caused by endothelial dysfunction plays a role in the pathogenesis of glaucoma.However,endothelial system accommodation is accomplished with the circulating EPCs. Objective The present trail was to investigate EPCs change in patients with primary acute angle-closure glaucoma (PACG)and explore the role of EPCs in the pathogenesis of PACG. Methods A prospective cohort study was designed.Thirty patients with PACG were enrolled in Tianjin Medical University General Hospital as PACG group,and 20 normal subjects served as control group.Periphery blood samples were obtained from all the patients and then stained with saturating concentrations of monoclonal antibodies,FITC-conjugated anti-CD34 and CD133 mAb.EPCs identified by CD34,CD133 were enumerated by flow cytometry,and the correlation between EPCs change and its relative factors was analyzed.Informed consent was obtained from each subject before any medical procedure. Results No significant differences were found in age,gender,vascular-related risk factor,blood biochemical indicators between PACG group and normal contol group(P＞0.05 ),but a higher intraocular pressure( IOP)was displayed in PACG group compared with normal control group ( P =0.00 ).The numbers of EPCs were ( 48 ± 22 ) cells/ml in PACG group and ( 65 ± 20 )cells/ml in normal control group with a significant difference between them (P=0.004).In PACG group,the numbers of EPCs were(60± 19 )cells/ml and (34 ±7 )cells/ml respeetively in phase 1 and phase 3 of optical nerve damage (Z=-3.015,P=0.002 ).There was a negative correlation between EPCs numbers and baseline IOP within a certain range( r=-0.835,P＜0.05 ).However,no obvious correlations were seen between EPCs numbers and blood lipid Level,blood glucose level or glaucoma course ( r =0.343,P =0.227 ; r =-0.203,P =0.419 ; r =0.198,P =0.610 ).The EPCs numbers in PACG patients with cardiovascular disease were(56±22)cells/ml and that of without PACG were (35± 15 ) cells/ml( P =0.005 ). Conclusions The numbers of EPCs decrease in PACG patient.These results imply that EPCs might play role during the restore of the optical nerve damage in PACG eye. Key words: Endothelial progenitor cell; Acute angle-closure glaucoma; Flow cytometry

Endothelial progenitor cells are associated with plasma homocysteine in coronary artery disease

Objective Little is known about the a ssociation between plasma homocysteine (Hcy) and e ndothelial progenitor cells (EPCs) in coronary artery disease (CAD).Methods Blood mononuclear cells were isolated from CAD (n = 30) patients and non-CAD controls (n = 30). Flow cytometric analysis and an in vitro c ulture system was used to evaluate the number and function of the EPC. Plasma homocysteine (Hcy) concentration was measured by an automated fl uorescence polarization immunoassay.Results Hcy level was higher in CAD than in non-CAD (13.69 ± 4.48 vs9.34 ± 2.31 μmol/L, P < 0.01). The number of circulating EPCs from CAD was decreased compared with non-CAD (58.7 ± 10.6 vs. 94.3 ± 15.1 cells/ml, P < 0.01). This decrease of EPCs in CAD was also detected (33.5 ± 6.9 vs. 55.9 ± 9.7 EPCs/×200 fi eld; P < 0.01) in an in vitroculture system. The numbers of circulating and diff erentiated EPCs were both inversely correlated with Hcy. EPCs from CAD were signifi cantly impaired in their migratory capacity and ability to adhere to fi bronectin.Conclusions We observed the correlation between Hcy level and EPC number, and also found an increased Hcy level in CAD patients. It will be interesting to reveal the underlying mechanisms contributing to the correlation and examine the possible causal relationship between Hcy levels and CAD.

Circulating endothelial progenitor cells in women with gestational alterations of glucose tolerance

Endothelial progenitor cells (EPCs) play a role in angiogenesis during pregnancy. The aim of this study was to evaluate circulating EPCs in pregnant women with gestational alterations of glucose tolerance. Glucose tolerance, insulin sensitivity and β-cell function were derived from oral glucose tolerance tests in 23 women with normal glucose tolerance (NGT), 18 with gestational impaired glucose tolerance (GIGT) and 24 with gestational diabetes mellitus (GDM). Circulating cells expressing CD34 in combination with CD133, kinase insert domain receptor (KDR) or both were quantified by flow cytometry. Women with GIGT and GDM had lower CD34(+)KDR(+) and CD34(+)CD133( +)KDR(+) cells at 27±3.2 weeks' gestation compared with NGT (ANOVA p<0.02 for both). CD34(+)KDR(+) and CD34(+)CD133(+)KDR(+) cells were inversely correlated with the area-under-the-glucose-curve (p<0.005, for both) and positively to insulin secretion-sensitivity index (p<0.05, for both). Alterations of glucose tolerance during pregnancy are associated with a decrease in EPCs. Hyperglycaemia might exert a direct effect on depletion of EPCs.

Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2

Diabetes mellitus type-2 (DM-2) contributes to atherogenesis by inducing endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In DM-2, the circulating EPC count is low and their functionality is impaired. The mechanisms that underlie this reduced count and impaired functionality are poorly understood. Nitric oxide (NO) is a short-lived signalling molecule that is produced by vascular endothelial cells and participates in the maintenance of vascular tone. NO is also known to participate in other physiological processes, such as cell survival, proliferation, and migration. The bioavailability of NO is reduced in EPCs from DM-2 patients. Interestingly, an inverse relationship exists between the reduction in NO bioavailability in EPCs and the patient's plasma glucose and glycated haemoglobin levels. In addition, NO bioavailability in EPCs correlates with plasma oxidized low-density lipoprotein levels in DM-2. Although this reduction in NO bioavailability could be attributed to oxidative stress in DM-2 patients, it also may be due to impairment of one or more members of the protein signalling cascades that are responsible for NO production. The stimulation of NO production or its signalling cascades in EPCs may increase their numbers and improve their function, thus attenuating endothelium damage, independent of the vasodilatory effects of NO. This review summarizes the metabolic alterations that underlie the molecular mechanisms that may be responsible for EPC decrease and dysfunction in DM-2 with emphasis on the involvement of the NO system.

The trend in the changing of human peripheral blood endothelial progenitor cells after brain infarction due to carotid atherosclerosis

Objective To investigate the trend in the changing of peripheral blood endothelial progenitor cells (EPCs) in patients with acute brain infarction due to atherosclerosis of internal carotid artery. Methods Peripheral blood samples of 30 adults were collected on the first 24 h, and 4, 7, 14 and 21 d after acute brain infarction. Mononuclear cells were collected. The expressions of CD34 and CD133 were detected by flow cytometry, and the number of EPCs was counted. Results There was significant difference in the number of peripheral blood EPCs among 3 groups at different time points (P = 0.000, for all). The number of peripheral blood EPCs was significantly lower in brain infarction group and carotid atherosclerosis group at 24 h than that in normal control group (P = 0.000, for all). The number of peripheral blood EPCs reduced to the lowest level at 7 d in brain infarction group (P = 0.001) and nearly approached to the level of that in carotid atherosclerosis group at 21 d (P = 0.901), but was still lower than normal range (P = 0.000). There was no relationship between the number changes of EPCs with platelet count (R2 = 0.852, P = 0.895) in the follow⁃up period. Conclusion Peripheral blood EPCs in patients with brain infarction due to carotid atherosclerosis is lower than normal level. At the acute stage of brain infarction, the bone marrow can be depressed, and amount of EPCs is consumed for repairing the injuried endothelium. Therefore, transient decrease of EPCs is observed at acute stage of brain infarction. DOI：10.3969/j.issn.1672-6731.2010.06.015

Circulating Levels of Endothelial Progenitor Cell Mobilizing Factors in the Metabolic Syndrome

Endothelial progenitor cells (EPCs) are an emerging biomarker of vascular health. However, there are few data on the biology and mobilizing factors of EPCs in metabolic syndrome (MS). The aim of this study was to assay EPC mobilizing factors, including granulocyte colony-stimulating factor, stem cell factor/c-kit ligand (SCF), vascular endothelial growth factor, and stromal cell-derived factor-1 levels, in patients with MS (n = 36) and age- and gender-matched controls (n = 38). There was a significant reduction of 83% in granulocyte colony-stimulating factor levels in patients with MS. Also, there were decreases in SCF and SCF soluble receptor levels. However, there was no significant difference in stromal cell-derived factor-1 levels, and paradoxically, vascular endothelial growth factor levels were increased, consistent with resistance. In conclusion, in addition to progenitor cell exhaustion as a mechanism for the decrease in EPCs in patients with MS, they also have a mobilization defect, as manifested by decreased levels of granulocyte colony-stimulating factor and SCF, resulting in a decrease in EPCs.

Endothelial Progenitor Cells(EPC) in Peripheral blood in Diabetic Foot with and without PAD.

Abstract 5130EPC is not very well defined population. These cells have either angiopoietic or angiostimulating function, the latter seems to be more relevant. It is well known thatMobilization of EPC to peripheral blood is decreased in diabetic rats. From the opposite, ischemia proved to stimulate mobilization. That is why, we decided to study EPC in diabetic patients with and without PAD Patients and methods40 pts with diabetes(type I- 4, type II-36) were studied. Duration of diabetes -1-46 years. The duration of more than 10 years was in 57% patients. Age- 49-73 years(mean age- 62 years). The patients were divided into two groups- diabetic foot without PAD(25 pts) – Group A, and diabetic foot with PAD- group B. PAD was diagnosed with sonography, duplex sonography and Rx arteriography. Normal volunteers were use as controls(mean age 51.6+2.0)CD34+ and CD133+ cells were numerated with CytoFlow(BD).5 Day CFU-Hill Colony Assay- non-adherent mononuclear cells (MNCs) was used to study EPCIn this method, peripheral blood MNCs are plated on fibronectin-coated dishes (6-well). After a 48 h pre-plating step to deplete the sample of adherent macrophages and mature endothelial cells, the non-adherent cells are removed and re-plated on fibronectin-coated dishes (24-well). Unique colonies that are formed in the 5 Day CFU-Hill Colony Assay are referred to as colony-forming unit-Hill colonies (CFU-Hill colonies) or colony-forming unit-ECs (CFU-ECs). Count the number of colonies per well for each sample. CFU-Hill colonies are defined as a central core of round cells with radiating elongated spindle-like cells at the periphery. Colonies without the CFU-Hill morphology may also be present but are not scored as CFU-Hill colonies. CFU-Hill Colonies are fixed with methanol and stained with a Giemsa solution. Plasma concentration of VEGF was studied by ELISA ResultsEPC colony forming ability in group A was 4.0+ 0.7, in group B-27.4+3.9. The differences between these two groups is highly significant(p 0.001). Low EPC level in diabetic neuropathy is probably related to decreased mobilization(G.Fadini e.a.2006). Rather unusual was higher EPC level in group B. It was shown that age-related decrease in EPC is due to decline in HIF-1 signaling(M. Hoenig e.a 2008). Probably, diabetic defect of mobilization is partly overcome with ischemia induced up-regulation of HIF-1 and VEGF. EPC in group B patients does not differ from controls(26.1+6.5).There were now correlations between EPC number and the number of either CD34+, CD133+, or KDR+ cells. We also failed to find any correlations between VEGF and EPC ConlusionEPC number in peripheral blood in diabetic patients without PAD is severely decreased. Diabetic patients with PAD have near normal EPC number. Thus, ischemia in diabetic patients is unable adequately mobilize EPC DisclosuresNo relevant conflicts of interest to declare.

The change and effect of endothelial progenitor cells in pig with multiple organ dysfunction syndromes

IntroductionThe dysfunction and decrease of endothelial progenitor cells (EPCs) may play a very important role in the initiation of organ dysfunction caused by trauma or severe sepsis. We aim to measure the number and function of EPCs in the progression of multiple organ dysfunction syndromes (MODS) caused by severe sepsis, which may help to understand the pathogenesis of MODS by the changing of EPCs.MethodsA total of 40 pigs were randomly divided into two groups, which were subjected to hemorrhagic shock, resuscitation and endotoxemia (experimental group, n = 20) or acted as a control (control group, n = 20). The number and function of EPCs including adhesive, migratory and angiogenesis capacities were analyzed at different times in both groups.ResultsAll the animals in the experimental group developed MODS (100%) and 17 of 20 animals (85%) died due to MODS; the incidence of MODS and death of the animals in the control group were 0% (P < 0.01). The number, migratory and adhesive capacities of EPCs decreased sharply in the animals of the experimental group corresponding to the increasing severities of MODS, but the angiogenesis function increased gradually until death. The decrease in function of EPCs preceded the decrease in number of EPCs. The decrease in number and function of EPCs occurred prior to the occurrence of MODS.ConclusionsFor the first time, it was observed that the number and function of EPCs decreased sharply in the progression of MODS and that it was prior to the occurrence of MODS. The decrease in number and function of EPCs may be one of the main pathogenic factors of MODS.

Homocysteine Reduces Endothelial Progenitor Cells in Stroke Patients through Apoptosis

Homocysteine (Hcy) is a risk factor for vascular dysfunction. High levels of Hcy may result in vascular injury accelerating atherosclerosis leading to ischemia. After ischemia, endothelial progenitor cells (EPCs) migrate from bone marrow to repair damaged sites either through direct incorporation of EPCs or by repopulating mature endothelial cells. This study looks into the relationship between increased Hcy in patients with cerebrovascular disease (CVD) and EPCs. Some patients with hyperhomocysteinemia were treated with B vitamins to evaluate if the treatment reverses the elevated Hcy and its impact on their EPC levels. EPCs were treated with Hcy to determine the in vitro effects of Hcy. Our clinical findings show that elevated Hcy levels have an inverse relationship with EPC levels and B vitamin intervention can reverse this effect. Our in vitro work shows that Hcy-mediated EPC toxicity is due to apoptosis involving caspase-8, cytochrome c release, and caspase-3 activation. Vitamin B(6), and B(9) significantly impair Hcy-mediated EPC caspase-3 activation in vitro. Our clinical and in vitro data together indicate that increased Hcy results in a decrease in EPC numbers. This decrease in EPC by Hcy may be occurring through increased apoptosis and B vitamins (B(6), B(9)) intervention can attenuate such effects.

Rheumatoid arthritis and cardiovascular disease

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting approximately 1% of the adult general population. Cardiovascular disease is recognized as the leading cause of death in RA patients, accounting for nearly 40% of their mortality. Patients with RA are at a twofold increased risk for myocardial infarction and stroke, with risk increasing to nearly threefold in patients who have had the disease for 10 years or more. Congestive heart failure appears to be a greater contributor to excess mortality than ischemia. This increased cardiovascular disease risk in RA patients seems to be independent of traditional cardiovascular risk factors. Pathogenic mechanisms include pro-oxidative dyslipidemia, insulin resistance, prothrombotic state, hyperhomocysteinemia, and immune mechanisms such as T-cell activation that subsequently lead to endothelial dysfunction, a decrease in endothelial progenitor cells, and arterial stiffness, which are the congeners of accelerated atherosclerosis observed in RA patients. This paper discusses pathogenic mechanisms, effects of methotrexate, tumor necrosis factor antagonists, steroids, and statins, with a perspective on therapy.

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development.

Simvastatin and rosuvastatin mobilize Endothelial Progenitor Cells but do not prevent their acute decrease during systemic inflammation

Introduction Endothelial Progenitor Cells (EPCs) are a specific subtype of haematopoietic stem cells that contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC counts in patients with stable coronary artery disease. Numbers of circulating EPCs decrease in various inflammatory diseases. Thus, we hypothesized that short term statin pre-treatment may alter the acute change in EPC levels during systemic inflammation. Objectives To explore the effect of statin pretreatment and low grade experimental endotoxemia on endothelial progenitor cells in humans. Materials and Methods Randomized, double-blind, placebo-controlled three way cross-over trial in six healthy male volunteers. Each volunteer received three treatments consisting of 5 days of oral simvastatin (80 mg/day), rosuvastatin (40 mg/day) or placebo. On Day 5 of each study period, subjects received lipopolysaccharide (LPS; 2 ng/kg i.v.). This trial has been registered with Clinical.Trials.gov, trial number NCT00309374. Results Statin pre-treatment led to a significant increase in circulating EPCs (1.9–3.5 fold, depending on statin and analytic method; P < 0.05) but could not suppress the endotoxemia induced EPC decrease (∼ − 75%; P < 0.05) during the observation period. Conclusions Statin therapy significantly increases EPCs within 96 hours and this may be a class effect. However, statins could not counteract the acute decrease in circulating EPCs after LPS infusion.

Patients with bisphosphonates‐associated osteonecrosis of the jaw have reduced circulating endothelial cells

Osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates is a newly described entity. To elucidate the mechanism leading to ONJ and to test the hypothesis that in patients with ONJ the bisphosphonates may interfere with endothelial cell proliferation, using flow cytometric analysis we evaluated the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in eight patients with bisphosphonate treatment and osteonecrosis, eight multiple myeloma (MM) patients with bisphosphonates treatment without ONJ and five normal subjects. MM patients showed an increase of CD34+ cells with respect the control subjects and ONJ subjects. EPCs and CECs were higher in MM patients compared to controls and ONJ patients. ONJ patients showed a decrease of EPCs compared to control subjects while CECs were similar to the controls group. Our results seem to show the possibility that bisphosphonates could have a antiangiogenic effect and a suppressive effect on CECs of patients with ONJ.

Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training

The number of hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is thought to be a marker for neovascularization and vascular repair. Because physical inactivity and aging are risk factors for cardiovascular diseases, these factors may influence the numbers of HSCs and EPCs. Therefore, we examined baseline and exercise-induced levels of HSCs and EPCs in sedentary and trained young and older men. To study the role of aging in eight sedentary young (19-28 years) and eight sedentary older men (67-76 years), baseline and acute exercise-induced numbers of HSCs (CD34+-cells) and EPCs (CD34+/VEGFR-2+-cells) were quantified by fluorescence-activated cell sorter (FACS) analysis. To examine the effect of chronic training, eight age-matched trained young men (18-28 years) were compared with sedentary young men, whereas older men performed an 8-week endurance training. Older men showed significantly lower baseline and exercise-induced levels of HSCs/EPCs than the young men (P < 0.05). In young and older men, acute exercise significantly increased HSCs (P < 0.01), but not EPCs. The absolute increase in numbers of HSCs was attenuated in older men (P = 0.03). Apart from the lower baseline numbers of EPCs after chronic training in older men, training status did not alter baseline or exercise-induced levels of HSCs/EPCs in young and older men. We concluded that advancing age results in lower circulating numbers of HSCs and EPCs and attenuates the acute exercise-induced increase in HSCs. Interestingly, in young as well as in older men chronic endurance training does not affect baseline and exercise-induced numbers of HSCs and EPCs.

Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy

Peripheral arterial disease (PAD) is a threatening complication of diabetes. As endothelial progenitor cells (EPCs) are involved in neovasculogenesis and maintenance of vascular homeostasis, their impairment may have a role in the pathogenesis of diabetic vasculopathy. This study aimed to establish whether number and function of EPCs correlate with PAD severity in type 2 diabetic patients. EPCs were defined by the expression of CD34, CD133 and KDR, and quantified by flow cytometry in 127 diabetic patients with and without PAD. PAD severity has been assessed as carotid atherosclerosis and clinical stage of leg atherosclerosis obliterans. Diabetic patients with PAD displayed a significant 53% reduction in circulating EPCs versus non-PAD patients, and EPC levels were negatively correlated with the degree of carotid stenosis and the stage of leg claudication. Moreover, the clonogenic and adhesion capacity of cultured EPCs were significantly lower in diabetic patients with PAD versus patients without. This study demonstrates that EPC decrease is related to PAD severity and that EPC function is altered in diabetic subjects with PAD, strengthening the pathogenetic role of EPC dysregulation in diabetic vasculopathy. EPC count may be considered a novel biological marker of peripheral atherosclerosis in diabetes.

Endothelial Progenitor Cells and Vascular Biology in Diabetes Mellitus: Current Knowledge and Future Perspectives

A growing amount of evidence demonstrates that Endothelial Progenitor Cells (EPCs) are involved in adult neovasculogenesis and maintenance of vascular integrity. EPC decrease and dysfunction are related to atherosclerosis and cardiovascular disease (CVD), and it has been proposed that the level of circulating EPCs may be used as a surrogate index of cumulative cardiovascular risk. Moreover, many experimental approaches reveal that exogenous EPC injection stimulates blood flow recovery in critical limb and myocardial ischemia, providing a new therapeutic tool for CVD. Diabetes Mellitus is a clinical condition characterized by a high incidence of CVD and is indeed associated with alterations in EPC physiology. In this review we focus on the relationships between EPCs and vascular biology, with particular regard to Diabetes Mellitus and future therapeutical implications.