High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia

Exposure to hypoxia induces changes in the structure and functional phenotypes of the cells composing the pulmonary vascular wall from larger to most peripheral vessels. Endothelial progenitor cells (EPCs) may be involved in vascular endothelial repair. Resident EPCs with a high proliferative potential are found in the pulmonary microcirculation. However, their potential location, identification, and functional role have not been clearly established. We investigated whether resident EPCs or bone marrow (BM)-derived EPCs play a major role in hypoxic response of pulmonary vascular endothelial cells (PVECs). Mice were exposed to hypoxia. The number of PVECs transiently decreased followed by an increase in hypoxic animals. Under hypoxic conditions for 1 wk, prominent bromodeoxyuridine incorporation was detected in PVECs. Some Ki67-positive cells were detected among PVECs after 1 wk under hypoxic conditions, especially in the capillaries. To clarify the origin of proliferating endothelial cells, we used BM chimeric mice expressing green fluorescent protein (GFP). The percentage of GFP-positive PVECs was low and constant during hypoxia in BM-transplanted mice, suggesting little engraftment of BM-derived cells in lungs under hypoxia. Proliferating PVECs in hypoxic animals showed increased expression of CD34, suggesting hypoxia-induced gene expression and cell surface antigen of EPC or stem/progenitor cells markers. Isolated PVECs from hypoxic mice showed colony- and tube-forming capacity. The present study indicated that hypoxia could induce proliferation of PVECs, and the origin of these cells might be tissue-resident EPCs.

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Surface-Bound Vascular Endothelial Growth Factor Promotes Prolonged Activation of Endothelial Cells: A New Technology for Capturing Endothelial Progenitor Cells by Intravascular Stents

Journal of Tissue Science & Engineering ◽

10.4172/2157-7552.1000140 ◽

2014 ◽

Vol 05 (02) ◽

Cited By ~ 2

Author(s):

Shotoku Tagawa Takehisa Matsuda

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

New Technology ◽

Vascular Endothelial ◽

Endothelial Progenitor ◽

Intravascular Stents ◽

Endothelial Growth Factor

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EFFECTS OF STRETCHED VASCULAR ENDOTHELIAL CELLS AND SMOOTH MUSCLE CELLS ON DIFFERENTIATION OF ENDOTHELIAL PROGENITOR CELLS

Journal of Mechanics in Medicine and Biology ◽

10.1142/s0219519413500504 ◽

2013 ◽

Vol 13 (02) ◽

pp. 1350050 ◽

Cited By ~ 1

Author(s):

ZHI-QIANG YAN ◽

YU-QING LI ◽

BIN-BIN CHENG ◽

QING-PING YAO ◽

LI-ZHI GAO ◽

...

Keyword(s):

Endothelial Cells ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Vascular Endothelial Cells ◽

Cyclic Strain ◽

Muscle Cells ◽

Endothelial Progenitor ◽

Vessel Injury

Differentiation of endothelial progenitor cells (EPCs) plays important roles in endothelial repair after vessel injury. Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and mechanical forces, including cyclic strain and shear stress, synergistically form the microenvironment of EPCs. However, the synergistic effect of cyclic strain, ECs, and VSMCs on the differentiation of EPCs remains unclear. In the present study, EPCs were indirectly co-cultured with stretched ECs or VSMCs that were subjected to 5%, 1.25-Hz cyclic strain by using FX-4000T Strain Unit. Then, Western blot and real-time PCR were used to examine expressions of EC marker, i.e., vascular cell adhesion molecule (VCAM), CD31, von Willebrand factor (vWF); VSMC markers, i.e., α-actin, Calponin, and SM22α; and signaling molecules, i.e., p-Akt and p-ERK. In static, co-cultured ECs increased expression of VCAM and phosphorylation of Akt and ERK in EPCs compared to that in EPCs cultured alone. In EPCs, co-cultured VSMCs decreased expressions of CD31 and vWF, but increased expressions of Calponin and SM22α. Stretched ECs reduced expressions of CD31 and vWF, enhanced Calponin and SM22α, and repressed phosphorylations of Akt and ERK in EPCs. Stretched VSMCs decreased CD31, increased Calponin and SM22α expressions, and repressed phosphorylation of Akt and ERK in EPCs. Our results suggest that ECs promoted EPC differentiation into ECs in static. VSMCs in static, as well as stretched ECs and stretched VSMCs, promoted EPC differentiation into VSMCs. Phosphorylation of Akt and ERK might be involved in EPC differentiation, mediated by the stretched ECs and VSMCs.

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The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease

European Journal of Applied Physiology ◽

10.1007/s00421-021-04876-1 ◽

2022 ◽

Author(s):

Panagiotis Ferentinos ◽

Costas Tsakirides ◽

Michelle Swainson ◽

Adam Davison ◽

Marrissa Martyn-St James ◽

...

Keyword(s):

Heart Failure ◽

Metabolic Disease ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

High Intensity ◽

Moderate Intensity ◽

Exercise Session ◽

Endothelial Progenitor ◽

Circulating Endothelial Progenitor Cells ◽

High Intensity Interval

AbstractCirculating 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. Objectives: to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Results: 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. Conclusion: the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term. Graphical abstract

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The comparison between two different exercise training programs on the mobilization of endothelial progenitor cells in patients with chronic heart failure

European Heart Journal ◽

10.1093/ehjci/ehaa946.1073 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Kourek ◽

K Psarra ◽

M Alshamari ◽

D Delis ◽

G Mitsiou ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Exercise Training ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Training Programs ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Endothelial Progenitor ◽

High Intensity Interval

Abstract Background Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are being used as an index of vascular endothelial function. Cardiac rehabilitation (CR) programs have been shown to stimulate the mobilization of EPCs in CHF patients. However, the effect of different exercise training programs on the EPCs in CHF patients has not been investigated. Purpose The purpose of the study was to assess the effect of 2 different exercise training programs on the mobilization of EPCs in patients with CHF and investigate if there were differences between them. Methods Forty-four consecutive patients (35 males) with stable CHF [mean±SD, Age (years): 56±10, EF (%): 33±8, Peak VO2 (ml/kg/min): 18.4±4.4] enrolled a 36-session CR program and they were randomized in one exercise training protocol; either high-intensity interval training (HIIT) or HIIT combined with muscle strength (COM). Venous blood was drawn at rest before and after the CR program. Five circulating endothelial populations were identified and quantified by flow cytometry (Table 1). EPCs values are expressed as cells/million enucleated cells in medians (25th-75th percentiles). Results In both HIIT and COM groups, the mobilization of all circulating endothelial populations increased after the CR program (p<0.05, Table 1). However, there was no difference in the mobilization of EPCs between HIIT and COM groups (p>0.05, Table 1). Conclusion A 36-session cardiac rehabilitation program increases the mobilization of endothelial progenitor cells in patients with chronic heart failure. High-intensity interval exercise training and HIIT combined with muscle strength have similar beneficial effect on endothelial progenitor cells, and therefore on vascular endothelial function. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project

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Abstract 9483: High Mobility Group Box 1 Promotes Angiogenesis From Bone Marrow-Derived Endothelial Progenitor Cells After Myocardial Infarction

Circulation ◽

10.1161/circ.130.suppl_2.9483 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Yuichi Nakamura ◽

Satoshi Suzuki ◽

Takeshi Shimizu ◽

Makiko Miyata ◽

Tetsuro Shishido ◽

...

Keyword(s):

Myocardial Infarction ◽

Bone Marrow ◽

Endothelial Cells ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Vascular Endothelial Cells ◽

High Mobility ◽

High Mobility Group ◽

Vascular Endothelial ◽

Double Positive

Background: High mobility group box 1 (HMGB1) is a DNA-binding protein secreted into extracellular space from necrotic cells and acts as a cytokine. We have reported that HMGB1 attenuates cardiac damage and restores cardiac function by enhancing angiogenesis after myocardial infarction (MI). We examined the role of HMGB1 in angiogenesis from bone marrow (BM) -derived cells in the heart, using transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-TG). Methods and Results: HMGB1-TG mice and wild-type littermate (WT) mice were lethally irradiated and injected with BM cells from green fluorescent protein (GFP) mice through the tail vein. Two weeks after BM transplantation, the left anterior descending artery was ligated to create MI. In flow cytometry analysis, GFP-positive cells were identified as donor BM cells-derived endothelial progenitor cells (EPC) if they were positive for both CD34 and CD144 in granulocyte differentiation antigen-1-negative fraction. Circulating EPC mobilized from BM was increased at 1 week after MI in HMGB1-TG mice compared with WT mice (41.9% vs. 24.5%, P < 0.01). Histological examination showed the size of MI was smaller in HMGB1-TG mice than in WT mice (42.9% vs. 59.1%, P < 0.01) at 4 weeks after MI. In myocardial immunofluorescence staining, GFP and CD31 double-positive cells were BM-derived cells engrafted within myocardial tissue as vascular endothelial cells of new capillaries or arterioles. The ratio of these double positive cells to all cardiac cells was significantly higher in the HMGB1-TG mice than in the WT mice (8.3% vs. 2.9%, P < 0.01). Enzyme-linked immunosorbent assay revealed that the levels of cardiac vascular endothelial growth factor at 1 week after MI were higher in HMGB1-TG mice than in WT mice (642.1 vs. 390.7 pg/dl, P < 0.05). Conclusions: The present study demonstrated the direct in vivo evidence that HMGB1 promoted angiogenesis and reduced MI size by enhancing mobilization and differentiation of BM cells to EPC, migration to the border zone of MI, and engraftment as vascular endothelial cells of new capillaries or arterioles in the infarcted heart.

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Comparison of the Effectiveness of High-Intensity Interval Training in Hypoxia and Normoxia in Healthy Male Volunteers: A Pilot Study

BioMed Research International ◽

10.1155/2019/7315714 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Aleksandra Żebrowska ◽

Dariusz Jastrzębski ◽

Ewa Sadowska-Krępa ◽

Marcin Sikora ◽

Camillo Di Giulio

Keyword(s):

Nitric Oxide ◽

Growth Factor ◽

High Intensity ◽

Hypoxia Inducible Factor ◽

Interval Training ◽

Vascular Endothelial ◽

High Intensity Interval Training ◽

Hypoxia Inducible Factor 1 ◽

High Intensity Interval ◽

Endothelial Growth Factor

Aims. The study investigated the effect of high-intensity interval training in hypoxia and normoxia on serum concentrations of proangiogenic factors, nitric oxide, and inflammatory responses in healthy male volunteers. Methods. Twelve physically active male subjects completed a high-intensity interval training (HIIT) in normoxia (NorTr) and in normobaric hypoxia (HypTr) (FiO2 = 15.2%). The effects of HIIT in hypoxia and normoxia on maximal oxygen uptake, hypoxia-inducible factor-1-alpha, vascular endothelial growth factor, nitric oxide, and cytokines were analyzed. Results. HIIT in hypoxia significantly increases maximal oxygen uptake (p=0.01) levels compared to pretraining levels. Serum hypoxia-inducible factor-1 (p=0.01) and nitric oxide levels (p=0.05), vascular endothelial growth factor (p=0.04), and transforming growth factor-β (p=0.01) levels were increased in response to exercise test after hypoxic training. There was no effect of training conditions for serum baseline angiogenic factors and cytokines (p>0.05) with higher HIF-1α and NO levels after hypoxic training compared to normoxic training (F = 9.1; p<0.01 and F = 5.7; p<0.05, respectively). Conclusions. High-intensity interval training in hypoxia seems to induce beneficial adaptations to exercise mediated via a significant increase in the serum concentrations of proangiogenic factors and serum nitric oxide levels compared to the same training regimen in normoxia.

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