This comprehensive review explores the multifaceted role of endothelial progenitor cells (EPCs) in vascular diseases, focusing on their involvement in the pathogenesis and their contributions to enhancing the efficacy of endovascular treatments for intracranial aneurysms (IAs). Initially discovered as CD34+ bone marrow-derived cells implicated in angiogenesis, EPCs have been linked to vascular repair, vasculogenesis, and angiogenic microenvironments. The origin and differentiation of EPCs have been subject to debate, challenging the conventional notion of bone marrow origin. Quantification methods, including CD34+ , CD133+ , and various assays, reveal the influence of factors, like age, gender, and comorbidities on EPC levels. Cellular mechanisms highlight the interplay between bone marrow and angiogenic microenvironments, involving growth factors, matrix metalloproteinases, and signaling pathways, such as phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). In the context of the pathogenesis of IAs, EPCs play a role in maintaining vascular integrity by replacing injured and dysfunctional endothelial cells. Recent research has also suggested the therapeutic potential of EPCs after coil embolization and flow diversion, and this has led the development of device surface modifications aimed to enhance endothelialization. The comprehensive insights underscore the importance of further research on EPCs as both therapeutic targets and biomarkers in IAs.

Physical inactivity is considered a significant risk factor for mortality and morbidity among chronic hemodialysis (HD) patients. Therefore, physical exercise is recommended in the treatment of HD patients. Although the beneficial effects of physical exercise in HD patients are well-described in the literature, the underlying physiological mechanisms still need to be fully understood. Recently, microRNAs (miRNAs) have emerged as potential mediators of the therapeutic effects of physical exercise in healthy individuals. miRNAs are short, single-stranded, noncoding RNAs involved in gene expression regulation. Specifically, upon forming the RNA-induced silencing complex, miRNAs selectively bind to specific miRNAs within cells, reducing gene expression. miRNAs can be secreted by cells in an accessible form or enclosed within exosomes or extracellular vesicles. They can be detected in various body fluids, including serum (circulating miRNAs), facilitating the study of their diverse expression. Currently, there is no available data regarding the impact of physical exercise on the expression of miRNAs involved in osteogenic differentiation, a fundamental mechanism in the development of vascular calcification, for HD patients. Therefore, we have designed an observational and longitudinal case-control study to evaluate the expression of miR-9 and miR-30b in HD patients participating in a 3-month interdialytic physical exercise program. This paper aims to present the study protocol and review the expression of circulating miRNAs in HD patients and their modulation through physical exercise.

Indirect revascularization is one of the main techniques for the treatment of Moyamoya disease. The formation of good collateral circulation is a key measure to improve cerebral blood perfusion and reduce the risk of secondary stroke, and is the main method for evaluating the effect of indirect revascularization. Therefore, how to predict and promote the formation of collateral circulation before and after surgery is important for improving the success rate of indirect revascularization in Moyamoya disease. Previous studies have shown that vascular endothelial growth factor, endothelial progenitor cells, Caveolin-1, and other factors observed in patients with Moyamoya disease may play a key role in the generation of collateral vessels after indirect revascularization through endothelial hyperplasia and smooth muscle migration. In addition, mutations in the genetic factor RNF213 have also been associated with this process. This study summarizes the factors and mechanisms influencing collateral circulation formation after indirect revascularization in Moyamoya disease.

Background: Exercise training improves endothelial function in patients with cardiovascular disease (CVD). However, the influence of training variables remains unclear. The aim of this study was to evaluate the effect of high-intensity interval training (HIIT), compared to moderate intensity training (MIT) and other exercise modalities (i.e., resistance and combined exercise), on endothelial function, assessed by arterial flow-mediated dilation (FMD) or endothelial progenitor cells (EPCs), in patients with CVD. Secondly, we investigated the influence of other training variables (i.e., HIIT protocol). Methods: The PICOS strategy was used to identify randomised and non-randomised studies comparing the effect of HIIT and other exercise modalities (e.g., MIT) on endothelial function in patients with CVD. Electronic searches were carried out in Pubmed, Embase, and Web of Science up to November 2022. The TESTEX scale was used to evaluate the methodological quality of the included studies. Random-effects models of between-group mean difference (MD) were estimated. A positive MD indicated an effect in favour of HIIT. Heterogeneity analyses were performed by the chi-square test and I 2 index. Subgroup analyses evaluated the influence of potential moderator variables. Results: Fourteen studies (13; 92.9% randomised) were included. Most of the studies trained 3 days a week for 12 weeks and performed long HIIT. No statistically significant differences were found between HIIT and MIT for improving brachial FMD in patients with coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) (8 studies; MD+ = 0.91% [95% confidence interval (CI) = -0.06, 1.88]). However, subgroup analyses showed that long HIIT (i.e., > 1 min) is better than MIT for enhancing FMD (5 studies; MD+ = 1.46% [95% CI = 0.35, 2.57]), while no differences were found between short HIIT (i.e., ≤ 1 min) and MIT (3 studies; MD+ = -0.41% [95% CI = -1.64, 0.82]). Insufficient data prevented pooled analysis for EPCs, and individual studies failed to find statistically significant differences (p > .050) between HIIT and other exercise modalities in increasing EPCs. Discussion: Poor methodological quality could limit the precision of the current results and increase the inconsistency. Long HIIT is superior to MIT for improving FMD in patients with CAD or HFrEF. Future studies comparing HIIT to other exercise modalities, as well as the effect on EPCs and in HF with preserved ejection fraction are required. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42022358156.

The objective of this meta-analysis was to systematically review existing evidence and evaluate variations in levels of circulating endothelial progenitor cells (EPCs) among individuals with psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA). Relevant studies were identified through database searches, and 20 records were enrolled. We used the fixed-effect model or random-effect model to estimate the pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) in circulating EPC levels between inflammatory arthritis patients and controls. The results showed that circulating EPC levels differed among subtypes of inflammatory arthritis, with significantly lower levels in patients with RA (SMD = -0.848, 95% CI = -1.474 to -0.221, p = 0.008) and PsA (SMD = -0.791, 95% CI = -1.136 to -0.446, p < 0.001). However, no statistically significant difference was found in circulating EPC levels between patients with JIA and controls (SMD = -1.160, 95% CI = -2.578 to 0.259, p = 0.109). Subgroup analyses suggested that in patients with RA, circulating EPC levels were influenced by age, disease activity, and duration. Although many studies have investigated circulating EPC levels in patients with inflammatory arthritis, the results have been inconsistent. This meta-analysis offers a comprehensive overview of the existing evidence and emphasizes the association between levels of circulating EPCs and various types of arthritis. However, further research is needed to determine the specific mechanisms underlying the observed differences in EPC levels in different types of arthritis and to establish the clinical utility of this biomarker.

In addition to its important transport functions, the skeletal system is involved in complex biological activities for the regulation of blood vessels. Endothelial progenitor cells (EPCs), as stem cells of endothelial cells (ECs), possess an effective proliferative capacity and a powerful angiogenic capacity prior to their differentiation. They demonstrate synergistic effects to promote bone regeneration and vascularization more effectively by co-culturing with multiple cells. EPCs demonstrate a significant therapeutic potential for the treatment of various bone diseases by secreting a combination of growth factors, regulating cellular functions, and promoting bone regeneration. In this review, we retrospect the definition and properties of EPCs, their interaction with mesenchymal stem cells, ECs, smooth muscle cells, and immune cells in bone regeneration, vascularization, and immunity, summarizing their mechanism of action and contribution to bone biology. Additionally, we generalized their role and potential mechanisms in the treatment of various bone diseases, possibly indicating their clinical application.

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.

Obstructive sleep apnea (OSA) is a respiratory condition during sleep caused by repeated pauses in breathing due to upper airway obstruction. It is estimated that OSA affects 30% of the population, but only 10% are well diagnosed due to the absence of a well-defined symptomatology and poor screening tools for early diagnosis. OSA is associated to an endothelial dysfunction inducing several biological responses such as hypoxia, hypercapnia and oxidative stress, among others. OSA also triggers respiratory, nervous, metabolic, humoral and immunity system activations that increase the possibility of suffering a cardiovascular (CV) disease. In this review, we expose different studies that show the relationship between OSA and endothelial dysfunction and its association with CV pathologies like hypertension, and we define the most well-known treatments and their limitations. Additionally, we describe the potential future directions in OSA research, and we report clinical features such as endothelial progenitor cell alterations that could act as biomarkers for the development of new diagnostic tools and target therapies.

The role of endothelial progenitor cells (EPCs) in atherosclerosis progression and neointimal growth after percutaneous coronary intervention (PCI) remains controversial. The purpose of this study was to perform a systematic review and meta-analysis of studies on EPCs in patients who had PCI.
We searched Pubmed, Embase and Cochrane databases and reviewed cited references up to August 31, 2021. Overall, we selected 9 studies, including 4612 patients.
Lower baseline EPC count was associated with a significantly greater occurrence of in-stent restenosis (HR 1.33; 95% CI 0.97-1.82, P = 0.045). As for EPC coating, there was no significant difference in the 1-year occurrence of cardiac death between EPCs-capturing drug-eluting stents (DES) and standard DES (Relative Risk [RR] 1.146; 95% CI 0.666-1.974, P = 0.98), but target lesion revascularization (RR 1.727; 95% CI: 1.199-2.487, P = 0.025), and target vessel failure (RR 1.591; 95% CI 1.213-2.088, P = 0.04) were significantly more common with EPCs-capturing DES than with standard DES.
Circulating EPC count might improve risk stratification after PCI, as it is correlated with the occurrence of in-stent restenosis. Currently available EPCs-capturing DES use was associated with an increased risk of 1-year adverse events, mainly driven by an increase in target lesion revascularization and target vessel failure, not cardiac death.

Endothelial colony-forming cells (ECFCs) hold significant promise as candidates for regenerative therapy of vascular injury. Existing studies remain largely preclinical and exhibit marked design heterogeneity. A systematic review of controlled preclinical trials of human ECFCs is needed to guide future study design and to accelerate clinical translation. A systematic search of Medline and EMBASE on 1 April 2019 returned 3131 unique entries of which 66 fulfilled the inclusion criteria. Most studies used ECFCs derived from umbilical cord or adult peripheral blood. Studies used genetically modified immunodeficient mice (n = 52) and/or rats (n = 16). ECFC phenotypes were inconsistently characterized. While >90% of studies used CD31+ and CD45-, CD14- was demonstrated in 73% of studies, CD146+ in 42%, and CD10+ in 35%. Most disease models invoked ischemia. Peripheral vascular ischemia (n = 29), central nervous system ischemia (n = 14), connective tissue injury (n = 10), and cardiovascular ischemia and reperfusion injury (n = 7) were studied most commonly. Studies showed predominantly positive results; only 13 studies reported ≥1 outcome with null results, three reported only null results, and one reported harm. Quality assessment with SYRCLE revealed potential sources of bias in most studies. Preclinical ECFC studies are associated with benefit across several ischemic conditions in animal models, although combining results is limited by marked heterogeneity in study design. In particular, characterization of ECFCs varied and aspects of reporting introduced risk of bias in most studies. More studies with greater focus on standardized cell characterization and consistency of the disease model are needed.