Our objective was to explore the effect of aerobic exercise on endothelial function in hypertensive and prehypertensive patients, and to ascertain the optimal duration and intensity of aerobic exercise. Data were synthesized using a random effects model to calculate the weighted mean difference (WMD) and 95% confidence interval (CI). Fifteen studies met the inclusion criteria. Aerobic exercise was found to significantly improve flow-mediated dilation (FMD) in prehypertensive and hypertensive patients (WMD, 2.23; 95% CI, 1.20-3.26; P  < 0.0001; I2  = 90%). Aerobic exercise, undertaken at a moderate or, even better, vigorous intensity, and lasting no less than 12 weeks, is an effective approach to improve flow-mediated dilation (FMD) in prehypertensive and hypertensive patients. The effect of aerobic exercise on endothelial function is influenced by participant characteristics: a better health status, a younger age, a larger basal body mass index, and a larger basal FMD were associated with larger improvement in FMD.

It remains controversial whether exercise training (EX) improves vascular endothelial function (VEF) independent of lipoprotein changes even though these are therapeutic goals for coronary artery disease (CAD).

The purpose of this study was to systematically review the effects of EX on VEF and blood lipid variables in patients with CAD.

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched five electronic databases (CINAHL, Embase, PubMed, SportDiscus, and Web of Science) until March 2024 for studies that met the following criteria: (i) patients with CAD aged ≥ 18 years; (ii) structured EX for ≥ 1 week in randomized or nonrandomized controlled studies; and (iii) measured brachial artery flow-mediated dilation (FMD) with or without blood lipid variables. We calculated effect sizes (ESs) and 95% confidence intervals (CIs) using a random-effects model and conducted subgroup analyses to identify the effect of training factors (duration, intensity, and weekly volume) on outcomes.

In total, 11 studies with 19 trials (629 patients, 60 ± 9 years) met the inclusion criteria. We conducted a separate meta-analysis for each of the four outcome measures: FMD (13 ESs), high-density lipoprotein-cholesterol (HDL-C; eight ESs), low-density lipoprotein cholesterol (LDL-C; eight ESs), and triglycerides (TGs; eight ESs). EX significantly increased FMD (mean ES 0.57; 95% CI 0.44-0.70; P < 0.001) and HDL-C levels (mean ES 0.25; 95% CI 0.12-0.39; P < 0.001) but had no effect on LDL-C and TG. Subgroup analyses for FMD found no significant variation in effect by training factor (duration, intensity, and weekly volume).

EX improves VEF with increased HDL-C, but we found no changes in LDL-C and TG in patients with CAD, suggesting that HDL-C is preferentially associated with exercise-induced VEF improvement.

Vascular endothelial cells form a single layer of flat cells that line the inner surface of blood vessels, extending from large vessels to the microvasculature of various organs. These cells are crucial metabolic and endocrine components of the body, playing vital roles in maintaining circulatory stability, regulating vascular tone, and preventing coagulation and thrombosis. Endothelial cell injury is regarded as a pivotal initiating factor in the pathogenesis of various diseases, triggered by multiple factors, including infection, inflammation, and hemodynamic changes, which significantly compromise vascular integrity and function. This review examines the causes, underlying molecular mechanisms, and potential therapeutic approaches for endothelial cell injury, focusing specifically on endothelial damage in cardiac ischemia/reperfusion (I/R) injury, sepsis, and diabetes. It delves into the intricate signaling pathways involved in endothelial cell injury, emphasizing the roles of oxidative stress, mitochondrial dysfunction, inflammatory mediators, and barrier damage. Current treatment strategies-ranging from pharmacological interventions to regenerative approaches and lifestyle modifications-face ongoing challenges and limitations. Overall, this review highlights the importance of understanding endothelial cell injury within the context of various diseases and the necessity for innovative therapeutic methods to improve patient outcomes.

Ruozhu Dai, Huilin Zhuo, Yangchun Chen, Kelian Zhang, Yongda Dong, Chengbo Chen and Wei Wang. Mechanism of isosorbide dinitrate combined with exercise training rehabilitation to mobilize endothelial progenitor cells in patients with coronary heart disease. Bioengineered. 2021 Nov. doi: 10.1080/21655979.2021.2000258.Since publication, significant concerns have been raised about the compliance with ethical policies for human research and the integrity of the data reported in the article.When approached for an explanation, the authors provided some original data but were not able to provide all the necessary supporting information. As verifying the validity of published work is core to the scholarly record's integrity, we are retracting the article. All authors listed in this publication have been informed.We have been informed in our decision-making by our editorial policies and the COPE guidelines.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted.'

Stem cells (SCs) play a crucial role in tissue repair, regeneration, and maintaining physiological homeostasis. Exercise mobilizes and enhances the function of SCs. This review examines the effects of acute and chronic aerobic and resistance exercise on the population of SCs in healthy and diseased individuals across different age groups. Both acute intense exercise and moderate regular training increase circulating precursor cells CD34+ and, in particular, the subset of angiogenic progenitor cells (APCs) CD34+/KDR+. Conversely, chronic exercise training has conflicting effects on circulating CD34+ cells and their function, which are likely influenced by exercise dosage, the health status of the participants, and the methodologies employed. While acute activity promotes transient mobilization, regular exercise often leads to an increased number of progenitors and more sustainable functionality. Short interventions lasting 10-21 days mobilize CD34+/KDR + APCs in sedentary elderly individuals, indicating the inherent capacity of the body to rapidly activate tissue-reparative SCs during activity. However, further investigation is needed to determine the optimal exercise regimens for enhancing SC mobilization, elucidating the underlying mechanisms, and establishing functional benefits for health and disease prevention. Current evidence supports the integration of intense exercise with chronic training in exercise protocols aimed at activating the inherent regenerative potential through SC mobilization. The physical activity promotes endogenous repair processes, and research on exercise protocols that effectively mobilize SCs can provide innovative guidelines designed for lifelong tissue regeneration. An artificial neural network (ANN) was developed to estimate the effects of modifying elderly individuals and implementing chronic resistance exercise on stem cell mobilization and its impact on individuals and exercise. The network's predictions were validated using linear regression and found to be acceptable compared to experimental results.

Cardiovascular diseases (CVD) stand at the forefront of global mortality, presenting an immense and urgent public health challenge on a global scale. Effectively addressing the associated risk factors is pivotal in not only preventing but also stabilizing and potentially reversing the progression of these conditions. Emerging research illuminates a compelling correlation between sleep disorders and CVD. Clinically, individuals afflicted with existing CVD or those possessing risk factors frequently grapple with sleep disturbances, exacerbating their conditions, particularly in severe cases where disease progression is accelerated. Even among ostensibly healthy individuals, chronic sleep deprivation exacts a toll on cardiovascular function. The strategic implementation of exercise interventions emerges as a potent tool in enhancing sleep quality, surpassing the efficacy of pharmaceutical treatments. Furthermore, the maintenance of optimal sleep patterns significantly contributes to lowering the risk of cardiovascular diseases. This comprehensive review delves deeply into the intricate relationship between exercise and the amelioration of cardiovascular disease risk associated with sleep. Moreover, it meticulously elucidates the complex mechanisms through which exercise operates, effectively reducing cardiovascular disease risk from the unique perspective of sleep science.

(1) Background: The declined function of peripheral circulating endothelial progenitor cells (EPCs) in aging individuals resulted in decreased endothelial cell regeneration and vascular endothelial function. Improving EPCs function in aging individuals plays an important role in preventing cardiovascular diseases. (2) Methods: Thirty aged (18-month-old) male Sprague-Dawley rats were randomly divided into control and exercise groups. An aerobic exercise intervention was performed 5 days/week for 8 weeks. EPCs functions, miR-21-5p, and TSP-1 expressions were detected after the intervention. The senescence rate, proliferation, and migration of EPCs were examined after overexpression of miR-21-5p and inhibition of TSP-1 expression. (3) Results: The senescence rate, proliferation, and migration of EPCs in exercise groups were significantly improved after exercise intervention. The miR-21-5p expression was increased and the TSP-1 mRNA expression was decreased in the EPCs after the intervention. miR-21-5p overexpression can improve EPCs function and inhibit TSP-1 expression but has no effect on senescence rate. Inhibition of TSP-1 expression could improve the function and reduce the senescence rate. (4) Conclusions: Our results indicate that long-term aerobic exercise can improve the functions of EPCs in aging individuals by downregulating TSP-1 expression via miR-21-5p, which reveals the mechanism of exercise in improving cardiovascular function.

Endothelial progenitor cells (EPCs) play a vital role in protecting endothelial dysfunction and cardiovascular disease (CVD). Physical exercise stimulates the mobilization of EPCs, and along with vascular endothelial growth factor (VEGF), promotes EPC differentiation, and contributes to vasculogenesis. The present meta-analysis examines the exercise-induced EPC mobilization and has an impact on VEGF in patients with CVD and healthy individuals. Database research was conducted (PubMed, EMBASE, Cochrane Library of Controlled Trials) by using an appropriate algorithm to indicate the exercise-induced EPC mobilization studies. Eligibility criteria included EPC measurements following exercise in patients with CVD and healthy individuals. A continuous random effect model meta-analysis (PROSPERO-CRD42019128122) was used to calculate mean differences in EPCs (between baseline and post-exercise values or between an experimental and control group). A total of 1460 participants (36 studies) were identified. Data are presented as standard mean difference (Std.MD) and 95% confidence interval (95% CI). Aerobic training stimulates the mobilization of EPCs and increases VEGF in patients with CVD (EPCs: Std.MD: 1.23, 95% CI: 0.70-1.76; VEGF: Std.MD: 0.76, 95% CI:0.16-1.35) and healthy individuals (EPCs: Std.MD: 1.11, 95% CI:0.53-1.69; VEGF: Std.MD: 0.75, 95% CI: 0.01-1.48). Acute aerobic exercise (Std.MD: 1.40, 95% CI: 1.00-1.80) and resistance exercise (Std.MD: 0.46, 95%CI: 0.10-0.82) enhance EPC numbers in healthy individuals. Combined aerobic and resistance training increases EPC mobilization (Std.MD:1.84, 95% CI: 1.03-2.64) in patients with CVD. Adequate exercise volume (>60%VO2max >30 min; P = 0.00001) yields desirable results. Our meta-analysis supports the findings of the literature. Exercise volume is required to obtain clinically significant results. Continuous exercise training of high-to-moderate intensity with adequate duration as well as combined training with aerobic and resistance exercise stimulates EPC mobilization and increases VEGF in patients with CVD and healthy individuals.

By definition, heart failure (HF) is a human pathological condition affecting the structure and function of all organs in the body, and the brain is not an exception to that. Failure of the heart to pump enough blood centrally and peripherally is at the foundation of HF patients' inability to attend even the most ordinary daily activities and progressive deterioration of their cognitive capacity. What is more, between heart and brain exists a bidirectional relationship that goes well beyond hemodynamics and concerns bioelectric and endocrine signaling. This increasingly consolidated evidence makes the scenario even more complex. Studies have mainly chased how HF impairs cognition without focusing much on preventive measures, notably cardio-cerebral health proxies. Here, we aim to provide a brief account of known and hypothetical factors that may explain how exercise can help obviate cognitive dysfunction associated with HF in its different forms. As we shall see, there is a stringent need for a deeper grasp of such mechanisms. Indeed, gaining this new knowledge will automatically shed new light on the inner workings of HF itself, thus resulting in more effective prevention and treatment of this escalating syndrome.

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs.

to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease.

Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed.

six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction.

the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term.

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs.

to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease.

Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed.

six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction.

the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term.

Endothelial progenitor cells (EPCs) play an important role in repairing damaged blood vessels and promoting neovascularization. However, the specific mechanism of EPCs promoting vascular repair is still unclear. Currently, there are two different views on the repair of damaged vessels by EPCs, one is that EPCs can directly differentiate into endothelial cells (ECs) and integrate into injured vessels, the other is that EPCs act on cells and blood vessels by releasing paracrine substances. But more evidence now supports the latter. Therefore, the paracrine mechanisms of EPCs are worth further study. This review describes the substances secreted by EPCs, some applications based on paracrine effects of EPCs, and the studies of paracrine mechanisms in cardiovascular diseases--all of these are to support the view that EPCs repair blood vessels through paracrine effects rather than integrating directly into damaged vessels.

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 70 years. The meta-analysis found that long-term (≥12 weeks) 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 12 weeks 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 12 weeks to reduce the risk of cardiovascular disease.

Exercise exerts direct effects on the vasculature via the impact of hemodynamic forces on the endothelium, thereby leading to functional and structural adaptations that lower cardiovascular risk. The patterns of blood flow and endothelial shear stress during exercise lead to atheroprotective hemodynamic stimuli on the endothelium and contribute to adaptations in vascular function and structure. The structural adaptations observed in arterial lumen dimensions after prolonged exercise supplant the need for acute functional vasodilatation in case of an increase in endothelial shear stress due to repeated exercise bouts. In contrast, wall thickness is affected by rather systemic factors, such as transmural pressure modulated during exercise by generalized changes in blood pressure. Several mechanisms have been proposed to explain the exercise-induced benefits in patients with coronary artery disease (CAD). They include decreased progression of coronary plaques in CAD, recruitment of collaterals, enhanced blood rheological properties, improvement of vascular smooth muscle cell and endothelial function, and coronary blood flow. This review describes how exercise via alterations in hemodynamic factors influences vascular function and structure which contributes to cardiovascular risk reduction, and highlights which mechanisms are involved in the positive effects of exercise on CAD.

Circulating progenitor cells (CPCs) play an important role in vascular repair and can influence cardiovascular (CV) health and longevity. Exercise is known to modulate these cells via mobilization from the bone marrow. The primary aims of this study were to evaluate the association of CPCs with mortality and explore the association between physical activity (PA) and CPCs.

1751 individuals from the Framingham Offspring cohort (66 ± 9 years [40-92 years], 54% female) were included in the study. CPCs (CD34^+, CD34⁺CD133⁺, CD34⁺CD133⁺KDR⁺) were measured by flow cytometry. Multivariable Cox regression analyses were performed to investigate relationship of CPCs with future CV event and mortality. Multivariate regression analyses were performed to determine the relationship between self-reported PA and CPC counts.

Following adjustment for standard risk factors, there was an inverse association between CD34⁺ CPCs and all-cause mortality (hazard ratio (HR) per unit increase in CD34⁺, 0.79; 95% CI 0.64-0.98, p = 0.036). CD34⁺CD133⁺ CPCs were inversely associated with CV mortality (HR 0.63, 95% CI 0.44-0.91, p = 0.013). Associations of CD34⁺ and CD34⁺CD133⁺ with mortality were strongest in participants with pre-existing CVD. PA was associated with CD34⁺ CPCs only in CVD participants (PA Index: β = 0.176, p = 0.003; moderate-to-vigorous [MVPA]: β = 0.159, p = 0.007). This relationship was maintained after adjustment for confounding variables.

A higher number of CD34⁺ and CD34⁺ CD133⁺ CPCs was inversely associated with all-cause and CV mortality. These associations were strongest in participants with CVD. PA is independently associated with CD34⁺ CPCs in individuals with CVD only, suggestive of greater benefit for this population group.

Heart failure with preserved ejection fraction (HFpEF) is currently lacking an effective pharmacological treatment with impact on major outcomes such as hospitalization and mortality. Exercise training (EXT) is recognized as an important nonpharmacological tool, capable of improving exercise capacity and quality of life, and has even been associated with a reduction in hospitalization and cardiovascular mortality risk. However, this positive impact largely lacks a physiological explanation. The aim of this narrative review was to provide an overview of the available data supporting the hypothesis that the beneficial role of EXT in HFpEF might be due to its effects on targeting the inflammatory paradigm described for this disease. A comprehensive literature search was conducted using the PubMed-NCBI database. We reviewed the effects of EXT throughout each step of the pathophysiological pathway leading to HFpEF and found clinical and/or preclinical evidence supporting the reduction of systemic inflammation, endothelial dysfunction, microvascular rarefaction, and myocardial stiffness. We also highlighted some gaps in the knowledge or topics that deserve further clarification in future studies. In conclusion, despite the scarcity of clinical studies in this population, there is compelling evidence suggesting that EXT modulates crucial aspects of the inflammatory pathway described for HFpEF and future investigation on cellular and molecular mechanisms are encouraged.

Exercise training has various benefits on cardiovascular health, and circulating angiogenic cells have been proposed as executing these changes. Work from the late 1990s supported an important role of these circulating post-natal cells in contributing to the maintenance and repair of the endothelium and vasculature. It was later found that circulating angiogenic cells were a heterogenous population of cells and primarily functioned in a paracrine manner by adhering to damaged endothelium and releasing growth factors. Many studies have discovered novel circulating angiogenic cell secreted proteins, microRNA and extracellular vesicles that mediate their angiogenic potential, and some studies have shown that both acute and chronic aerobic exercise training have distinct benefits. This review highlights work establishing an essential role of secreted factors from circulating angiogenic cells and summarizes studies regarding the effects of exercise training on these factors. Finally, we highlight the various gaps in the literature in hopes of guiding future work.

Endothelial progenitor cells (EPCs) play an important role in the re-endothelialization of ischemic cerebrovascular disease. However, the current acquisition method has some deficiencies. This study aimed to design a new and practical method for obtaining EPCs.

Bone marrow was obtained autologously from the right tibia of living rats. Briefly, the right tibia bone was carefully exposed and two holes (1 mm in diameter) were made in the tuberosity and lower one-third of the tibia, respectively. A PE-50 catheter and syringe (5 mL) were inserted through the holes to aspirate the bone marrow. Bone marrow mononuclear cells (BMMCs) were isolated by density-gradient centrifugation with Ficoll and counted. Adherent cell culture continued for 2 weeks, and the medium was replaced every 3 days.

During the first days of culture, adherent cells formed a monolayer, consisting predominantly of small-sized cells. Single large cells with endothelial morphology were observed. On day 4, the nonadherent cells were removed, and the adherent cells were left for further culture. On day 6-7, a proliferating population of round cells formed clusters in the culture chamber, and morphological analysis revealed a homogeneous population of colony-forming units (CFUs). Large, flat cells with endothelial morphology sprouted from the CFUs, which had nearly disappeared by day 14 of culture. The adherent cells were positive for CD133 and vascular endothelial growth factor receptor 2 (VEGFR2), internalized acetylated low-density lipoprotein, and bound ulex europaeus-agglutinin-I, but were negative for CD45, which correlated with the endothelial morphology and ability to form capillaries of EPCs.

Our results are direct evidence that mononuclear cells (MCS) from living rat bone marrow can be used to culture EPCs in vitro under certain culture conditions, providing a new method for the further study of autologous EPC transplantation.