16 results on '"Kushner EJ"'
Search Results
2. Lipidure-based micropattern fabrication for stereotyping cell geometry.
- Author
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Grespin DB, Niven TG, Babson RO, and Kushner EJ
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- Cell Adhesion, Stereotyping, Cytoskeleton
- Abstract
Cell autonomous behaviors such as migration and orchestration of cell polarity programs are required for physiological tissue formation. Micropatterns are cell-adhesive shapes that confine cell(s) to a user defined geometry. This biophysical confinement allows researchers to standardize the cell shape, and in doing so, stereotype organelle and cytoskeletal systems that can have an arbitrary organization. Thus, micropatterning can be a powerful tool in interrogation of polarity programs by enforcing a homogenous cell shape and cytoskeletal organization. A major drawback of this approach is the equipment and reagent costs associated with fabrication. Here, we provide a characterization of a compound called Lipidure (2-Methacryloyloxy ethyl phosphorylcholine) that is up to 40X less expensive than other cell repulsive coating agents. We found that Lipidure is an effective cell-repulsive agent for photolithography-based micropattern fabrication. Our results demonstrate that Lipidure is sensitive to deep UV irradiation for photolithography masking, stable in both benchtop and aqueous environments, non-toxic in prolonged culture, and effective at constraining cell geometry for quantification of cytoskeletal systems., (© 2023. The Author(s).)
- Published
- 2023
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3. Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis.
- Author
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Francis CR, Kincross H, and Kushner EJ
- Subjects
- Guanine Nucleotide Exchange Factors metabolism, rab GTP-Binding Proteins genetics, rab GTP-Binding Proteins metabolism, Actins metabolism, Endothelial Cells metabolism
- Abstract
In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35's primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence, apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization through limiting Rac1 and RhoA activity, which is required to set up proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent brake of actin remodeling during blood vessel development., (© 2022. The Author(s).)
- Published
- 2022
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4. Synaptotagmin-Like Protein 2a Regulates Angiogenic Lumen Formation via Weibel-Palade Body Apical Secretion of Angiopoietin-2.
- Author
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Francis CR, Claflin S, and Kushner EJ
- Subjects
- Angiopoietin-2 genetics, Animals, Animals, Genetically Modified, Cells, Cultured, Humans, Membrane Proteins genetics, Receptor, TIE-2 metabolism, Signal Transduction, Weibel-Palade Bodies genetics, Zebrafish genetics, Zebrafish Proteins genetics, rab27 GTP-Binding Proteins metabolism, Angiopoietin-2 metabolism, Exocytosis, Human Umbilical Vein Endothelial Cells metabolism, Membrane Proteins metabolism, Neovascularization, Physiologic, Weibel-Palade Bodies metabolism, Zebrafish Proteins metabolism
- Abstract
[Figure: see text].
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- 2021
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5. Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication.
- Author
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Yu Z, Mouillesseaux KP, Kushner EJ, and Bautch VL
- Subjects
- Animals, Cells, Cultured, Centrosome drug effects, Centrosome metabolism, Down-Regulation drug effects, Down-Regulation genetics, Endothelial Cells drug effects, Endothelial Cells metabolism, Endothelial Cells ultrastructure, Female, Human Umbilical Vein Endothelial Cells, Humans, Mice, Neoplasms blood supply, Neoplasms metabolism, RNA Interference, RNA, Small Interfering pharmacology, Tumor Suppressor Protein p53 antagonists & inhibitors, Centrosome physiology, Endothelial Cells physiology, Neoplasms genetics, Neoplasms pathology, Tumor Suppressor Protein p53 genetics
- Abstract
Approximately 30% of tumor endothelial cells have over-duplicated (>2) centrosomes, which may contribute to abnormal vessel function and drug resistance. Elevated levels of vascular endothelial growth factor A induce excess centrosomes in endothelial cells, but how other features of the tumor environment affect centrosome over-duplication is not known. To test this, we treated endothelial cells with tumor-derived factors, hypoxia, or reduced p53, and assessed centrosome numbers. We found that hypoxia and elevated levels of bone morphogenetic protein 2, 6 and 7 induced excess centrosomes in endothelial cells through BMPR1A and likely via SMAD signaling. In contrast, inflammatory mediators IL-8 and lipopolysaccharide did not induce excess centrosomes. Finally, down-regulation in endothelial cells of p53, a critical regulator of DNA damage and proliferation, caused centrosome over-duplication. Our findings suggest that some tumor-derived factors and genetic changes in endothelial cells contribute to excess centrosomes in tumor endothelial cells., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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6. Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6.
- Author
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Mouillesseaux KP, Wiley DS, Saunders LM, Wylie LA, Kushner EJ, Chong DC, Citrin KM, Barber AT, Park Y, Kim JD, Samsa LA, Kim J, Liu J, Jin SW, and Bautch VL
- Subjects
- Animals, Bone Morphogenetic Proteins genetics, Cell Line, Human Umbilical Vein Endothelial Cells, Humans, Mice, Receptors, Notch genetics, Smad6 Protein genetics, Zebrafish, Bone Morphogenetic Proteins metabolism, Neovascularization, Physiologic physiology, Receptors, Notch metabolism, Smad6 Protein metabolism
- Abstract
Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation.
- Published
- 2016
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7. Excess centrosomes perturb dynamic endothelial cell repolarization during blood vessel formation.
- Author
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Kushner EJ, Ferro LS, Yu Z, and Bautch VL
- Subjects
- Actin Cytoskeleton, Actins, Actomyosin, Blood Vessels metabolism, Blood Vessels physiology, Cell Culture Techniques, Cell Polarity physiology, Cytoskeleton, Dyneins, Humans, Microtubules metabolism, Tubulin, rac1 GTP-Binding Protein genetics, rac1 GTP-Binding Protein metabolism, Centrosome metabolism, Centrosome physiology, Endothelial Cells metabolism
- Abstract
Blood vessel formation requires dynamic movements of endothelial cells (ECs) within sprouts. The cytoskeleton regulates migratory polarity, and centrosomes organize the microtubule cytoskeleton. However, it is not well understood how excess centrosomes, commonly found in tumor stromal cells, affect microtubule dynamics and interphase cell polarity. Here we find that ECs dynamically repolarize during sprouting angiogenesis, and excess centrosomes block repolarization and reduce migration and sprouting. ECs with excess centrosomes initially had more centrosome-derived microtubules but, paradoxically, fewer steady-state microtubules. ECs with excess centrosomes had elevated Rac1 activity, and repolarization was rescued by blockade of Rac1 or actomyosin blockers, consistent with Rac1 activity promoting cortical retrograde actin flow and actomyosin contractility, which precludes cortical microtubule engagement necessary for dynamic repolarization. Thus normal centrosome numbers are required for dynamic repolarization and migration of sprouting ECs that contribute to blood vessel formation., (© 2016 Kushner et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)
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- 2016
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8. LGN Directs Interphase Endothelial Cell Behavior via the Microtubule Network.
- Author
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Wright CE, Kushner EJ, Du Q, and Bautch VL
- Subjects
- Endothelium, Vascular metabolism, Human Umbilical Vein Endothelial Cells, Humans, Neovascularization, Physiologic, Endothelium, Vascular cytology, Interphase, Intracellular Signaling Peptides and Proteins physiology, Microtubules metabolism
- Abstract
Angiogenic sprouts require coordination of endothelial cell (EC) behaviors as they extend and branch. Microtubules influence behaviors such as cell migration and cell-cell interactions via regulated growth and shrinkage. Here we investigated the role of the mitotic polarity protein LGN in EC behaviors and sprouting angiogenesis. Surprisingly, reduced levels of LGN did not affect oriented division of EC within a sprout, but knockdown perturbed overall sprouting. At the cell level, LGN knockdown compromised cell-cell adhesion and migration. EC with reduced LGN levels also showed enhanced growth and stabilization of microtubules that correlated with perturbed migration. These results fit a model whereby LGN influences interphase microtubule dynamics in endothelial cells to regulate migration, cell adhesion, and sprout extension, and reveal a novel non-mitotic role for LGN in sprouting angiogenesis.
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- 2015
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9. Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development.
- Author
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Klein KR, Karpinich NO, Espenschied ST, Willcockson HH, Dunworth WP, Hoopes SL, Kushner EJ, Bautch VL, and Caron KM
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- Animals, Cell Movement, Cell Proliferation, Female, HEK293 Cells, Humans, Ligands, Male, Mice, Mice, Knockout, Muscle Cells cytology, Oligonucleotide Array Sequence Analysis, Phenotype, Receptors, CXCR genetics, Signal Transduction, Adrenomedullin metabolism, Gene Expression Regulation, Developmental, Heart embryology, Lymphatic Vessels embryology, Receptors, CXCR physiology
- Abstract
Atypical 7-transmembrane receptors, often called decoy receptors, act promiscuously as molecular sinks to regulate ligand bioavailability and consequently temper the signaling of canonical G protein-coupled receptor (GPCR) pathways. Loss of mammalian CXCR7, the most recently described decoy receptor, results in postnatal lethality due to aberrant cardiac development and myocyte hyperplasia. Here, we provide the molecular underpinning for this proliferative phenotype by demonstrating that the dosage and signaling of adrenomedullin (Adm, gene; AM, protein)-a mitogenic peptide hormone required for normal cardiovascular development-is tightly controlled by CXCR7. To this end, Cxcr7(-/-) mice exhibit gain-of-function cardiac and lymphatic vascular phenotypes that can be reversed upon genetic depletion of adrenomedullin ligand. In addition to identifying a biological ligand accountable for the phenotypes of Cxcr7(-/-) mice, these results reveal a previously underappreciated role for decoy receptors as molecular rheostats in controlling the timing and extent of GPCR-mediated cardiac and vascular development., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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10. Excess centrosomes disrupt endothelial cell migration via centrosome scattering.
- Author
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Kushner EJ, Ferro LS, Liu JY, Durrant JR, Rogers SL, Dudley AC, and Bautch VL
- Subjects
- Animals, Blood Vessels pathology, Blood Vessels ultrastructure, Centrosome ultrastructure, Golgi Apparatus metabolism, Human Umbilical Vein Endothelial Cells, Humans, Interphase, Mice, Mice, Transgenic, Microtubules metabolism, Microtubules ultrastructure, Tumor Cells, Cultured, Cell Movement, Centrosome physiology, Endothelial Cells ultrastructure
- Abstract
Supernumerary centrosomes contribute to spindle defects and aneuploidy at mitosis, but the effects of excess centrosomes during interphase are poorly understood. In this paper, we show that interphase endothelial cells with even one extra centrosome exhibit a cascade of defects, resulting in disrupted cell migration and abnormal blood vessel sprouting. Endothelial cells with supernumerary centrosomes had increased centrosome scattering and reduced microtubule (MT) nucleation capacity that correlated with decreased Golgi integrity and randomized vesicle trafficking, and ablation of excess centrosomes partially rescued these parameters. Mechanistically, tumor endothelial cells with supernumerary centrosomes had less centrosome-localized γ-tubulin, and Plk1 blockade prevented MT growth, whereas overexpression rescued centrosome γ-tubulin levels and centrosome dynamics. These data support a model whereby centrosome-MT interactions during interphase are important for centrosome clustering and cell polarity and further suggest that disruption of interphase cell behavior by supernumerary centrosomes contributes to pathology independent of mitotic effects., (© 2014 Kushner et al.)
- Published
- 2014
- Full Text
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11. CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7/RhoA-mediated pathway.
- Author
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Charpentier MS, Christine KS, Amin NM, Dorr KM, Kushner EJ, Bautch VL, Taylor JM, and Conlon FL
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- Animals, Blotting, Western, Calcium-Binding Proteins, Cell Adhesion, Cell Differentiation, Cell Proliferation, Cells, Cultured, Chromatin Immunoprecipitation, DNA-Binding Proteins genetics, EGF Family of Proteins, Embryo, Nonmammalian cytology, Embryonic Development, Endothelial Growth Factors genetics, Endothelium, Vascular metabolism, Extracellular Matrix Proteins genetics, Female, Fluorescent Antibody Technique, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells metabolism, Humans, Immunoenzyme Techniques, Molecular Sequence Data, Transcription Factors genetics, Transcription, Genetic, Xenopus Proteins genetics, Xenopus laevis growth & development, rhoA GTP-Binding Protein genetics, DNA-Binding Proteins metabolism, Embryo, Nonmammalian metabolism, Endothelial Growth Factors metabolism, Endothelium, Vascular cytology, Extracellular Matrix Proteins metabolism, Gene Expression Regulation, Morphogenesis physiology, Transcription Factors metabolism, Xenopus Proteins metabolism, Xenopus laevis metabolism, rhoA GTP-Binding Protein metabolism
- Abstract
The formation of the vascular system is essential for embryonic development and homeostasis. However, transcriptional control of this process is not fully understood. Here we report an evolutionarily conserved role for the transcription factor CASZ1 (CASTOR) in blood vessel assembly and morphogenesis. In the absence of CASZ1, Xenopus embryos fail to develop a branched and lumenized vascular system, and CASZ1-depleted human endothelial cells display dramatic alterations in adhesion, morphology, and sprouting. Mechanistically, we show that CASZ1 directly regulates Epidermal Growth Factor-Like Domain 7 (Egfl7). We further demonstrate that defects of CASZ1- or EGFL7-depleted cells are in part due to diminished RhoA expression and impaired focal adhesion localization. Moreover, these abnormal endothelial cell behaviors in CASZ1-depleted cells can be rescued by restoration of Egfl7. Collectively, these studies show that CASZ1 is required to directly regulate an EGFL7/RhoA-mediated pathway to promote vertebrate vascular development., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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12. Prehypertension and endothelial progenitor cell function.
- Author
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MacEneaney OJ, DeSouza CA, Weil BR, Kushner EJ, Van Guilder GP, Mestek ML, Greiner JJ, and Stauffer BL
- Subjects
- Apoptosis physiology, Case-Control Studies, Caspase 3 metabolism, Cell Movement physiology, Colony-Forming Units Assay, Female, Humans, Male, Middle Aged, Endothelium, Vascular cytology, Prehypertension blood, Stem Cells cytology, Stem Cells physiology
- Abstract
Prehypertension is associated with significant damage to the coronary vasculature and increased rates of adverse cardiovascular events. Circulating endothelial progenitor cells (EPCs) are critical to vascular repair and the formation of new blood vessels. We tested the hypothesis that prehypertension is associated with EPC dysfunction. Peripheral blood samples were collected from 83 middle-aged and older adults (51 male and 32 female): 40 normotensive subjects (age 53±2 years; BP 111/74±1/1 mm Hg) and 43 prehypertensive subjects (age 54±2 years; 128/77±1/1 mm Hg). EPCs were isolated from peripheral blood, and EPC colony-forming capacity (colony-forming unit (CFU) assay), migratory activity (Boyden chamber) and apoptotic susceptibility (active caspase-3 concentrations) were determined. There were no significant differences in the number of EPC CFUs (10±2 vs 9±1), EPC migration (1165±82 vs 1120±84 fluorescent units) or active intracellular caspase-3 concentrations (2.7±0.3 vs 2.3±0.2 ng ml⁻¹) between the normotensive and prehypertensive groups. When groups were stratified into low prehypertension (n=27; systolic blood pressure: 120-129 mm Hg) and high prehypertension (n=16; 130-139 mm Hg), it was found that EPCs from the high prehypertensive group produced fewer (∼65%, P<0.05) CFUs compared with the low prehypertensive (4±1 vs 12±2) and normotensive adults. In conclusion, EPC colony-forming capacity is impaired only in prehypertensive adults with systolic BP greater than 130 mm Hg. Prehypertension is not associated with migratory dysfunction or enhanced apoptosis of EPCs.
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- 2011
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13. Human aging and CD31+ T-cell number, migration, apoptotic susceptibility, and telomere length.
- Author
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Kushner EJ, Weil BR, MacEneaney OJ, Morgan RG, Mestek ML, Van Guilder GP, Diehl KJ, Stauffer BL, and DeSouza CA
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- Adult, Age Factors, Aged, Aging genetics, Aging metabolism, Aging pathology, Cardiovascular Diseases genetics, Cardiovascular Diseases metabolism, Cardiovascular Diseases pathology, Caspase 3 metabolism, Cell Separation methods, Chemokine CXCL12 metabolism, Cytochromes c metabolism, Flow Cytometry, Humans, Lymphocyte Count, Male, Middle Aged, Risk Factors, T-Lymphocyte Subsets pathology, T-Lymphocytes pathology, Telomerase metabolism, Vascular Endothelial Growth Factor A metabolism, Young Adult, Aging immunology, Apoptosis genetics, Cardiovascular Diseases immunology, Chemotaxis, Platelet Endothelial Cell Adhesion Molecule-1 analysis, T-Lymphocyte Subsets immunology, T-Lymphocytes immunology, Telomere metabolism
- Abstract
CD31(+) T cells, or so-called "angiogenic T cells," have been shown to demonstrate vasculoprotective and neovasculogenic qualities. The influence of age on CD31(+) T-cell number and function is unclear. We tested the hypothesis that circulating CD31(+) T-cell number and migratory capacity are reduced, apoptotic susceptibility is heightened, and telomere length is shortened with advancing age in adult humans. Thirty-six healthy, sedentary men were studied: 12 young (25 ± 1 yr), 12 middle aged (46 ± 1 yr), and 12 older (64 ± 2 yr). CD31(+) T cells were isolated from peripheral blood samples by magnetic-activated cell sorting. The number of circulating CD31(+) T cells (fluorescence-activated cell sorting analysis) was lower (P < 0.01) in older (24% of CD3(+) cells) compared with middle-aged (38% of CD3(+) cells) and young (40% of CD3(+) cells) men. Migration (Boyden chamber) to both VEGF and stromal cell-derived factor-1α was markedly blunted (P < 0.05) in cells harvested from middle-aged [306.1 ± 45 and 305.6 ± 46 arbitrary units (AU), respectively] and older (231 ± 65 and 235 ± 62 AU, respectively) compared with young (525 ± 60 and 570 ± 62 AU, respectively) men. CD31(+) T cells from middle-aged and older men demonstrated greater apoptotic susceptibility, as staurosporine-stimulated intracellular caspase-3 activation was ∼ 40% higher (P < 0.05) than young. There was a progressive age-related decline in CD31(+) T-cell telomere length (young: 10,706 ± 220 bp; middle-aged: 10,179 ± 251 bp; and older: 9,324 ± 192 bp). Numerical and functional impairments in this unique T-cell subpopulation may contribute to diminished angiogenic potential and greater cardiovascular risk with advancing age.
- Published
- 2010
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14. Endothelial progenitor cell function, apoptosis, and telomere length in overweight/obese humans.
- Author
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MacEneaney OJ, Kushner EJ, Westby CM, Cech JN, Greiner JJ, Stauffer BL, and DeSouza CA
- Subjects
- Adult, Aged, Apoptosis drug effects, Cell Movement, Chemokine CXCL12 metabolism, Cytochromes c metabolism, Enzyme Inhibitors pharmacology, Granulocyte Colony-Stimulating Factor metabolism, Humans, Middle Aged, Obesity metabolism, Plant Lectins pharmacology, Staurosporine pharmacology, Telomere, Vascular Endothelial Growth Factor A metabolism, Apoptosis physiology, Caspase 3 metabolism, Cytokines metabolism, Endothelial Cells physiology, Obesity physiopathology, Stem Cells physiology
- Abstract
Excess adiposity is associated with increased cardiovascular morbidity and mortality. Endothelial progenitor cells (EPCs) play an important role in vascular repair. We tested the hypothesis that increased adiposity is associated with EPC dysfunction, characterized by diminished capacity to release angiogenic cytokines, increased apoptotic susceptibility, reduced cell migration, and shorter telomere length. A total of 67 middle-aged and older adults (42-67 years) were studied: 25 normal weight (normal weight; BMI: 18.5-24.9 kg/m(2)) and 42 overweight/obese (overweight/obese; BMI: 25.0-34.9 kg/m(2)). Cells with phenotypic EPC characteristics were isolated from peripheral blood. EPC release of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF) was determined in the absence and presence of phytohemagglutinin (10 microg/ml). Intracellular active caspase-3 and cytochrome c concentrations were determined by immunoassay. Migratory activity of EPCs in response to VEGF (2 ng/ml) and stromal cell-derived factor-1alpha (SDF-1alpha; 10 ng/ml) was determined by Boyden chamber. Telomere length was assessed by Southern hybridization. Phytohemagglutinin-stimulated release of VEGF (90.6 +/- 7.6 vs. 127.2 +/- 11.6 pg/ml) and G-CSF (896.1 +/- 77.4 vs. 1,176.3 +/- 126.3 pg/ml) was ~25% lower (P < 0.05) in EPCs from overweight/obese vs. normal weight subjects. Staurosporine induced a ~30% greater (P < 0.05) increase in active caspase-3 in EPCs from overweight/obese (2.8 +/- 0.2 ng/ml) compared with normal weight (2.2 +/- 0.2) subjects. There were no significant differences in EPC migration to either VEGF or SDF-1alpha. Telomere length did not differ between groups. These results indicate that increased adiposity adversely affects the ability of EPCs to release proangiogenic cytokines and resist apoptosis, potentially compromising their reparative potential.
- Published
- 2010
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15. Transcriptional regulation of beta2-microglobulin demonstrated via a novel genomic and proteomic analysis of percutaneously collected peripheral atheroma.
- Author
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Stauffer BL, Kushner EJ, Wulfman T, Zeller T, Sobus R, and Westby CM
- Subjects
- Atherosclerosis genetics, Electrophoresis, Gel, Two-Dimensional, Humans, RNA, Messenger analysis, Transcription, Genetic, beta 2-Microglobulin analysis, Atherosclerosis metabolism, Genomics, Proteomics, beta 2-Microglobulin genetics
- Published
- 2008
- Full Text
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16. Gender and Endothelial Progenitor Cell Number in Middle-Aged Adults.
- Author
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Stauffer BL, Maceneaney OJ, Kushner EJ, Cech JN, Greiner JJ, Westby CM, and Desouza CA
- Abstract
BACKGROUND: Between the ages of 45 and 65 years, the prevalence of cardiovascular disease is significantly lower in women compared with men. Circulating bone marrow-derived endothelial progenitor cells (EPCs) play an important role in vascular repair. Reduced EPC number is predictive of more cardiovascular events. It is currently unknown whether there is a sex-difference in EPC number in middle-aged adults. OBJECTIVE: We tested the hypothesis that circulating EPC number is higher in middle-aged women than men. METHODS: Peripheral blood samples were collected from 58 sedentary adults, 29 men (57 ± 1 yr) and 29 women (58 ± 1 yr). Mononuclear cells were isolated and fluorescence-activated cell sorting (FACS) analysis of cells negative for CD45 was performed for those positive for CD34, and triple positive for CD34, VEGFR-2, and CD133 according to the recommendations of the International Society for Hematotherapy and Graft Engineering. RESULTS: The number of CD45(-)/CD34(+) and CD45(-)/CD34(+)/ VEGFR-2(+)/CD133(+) were not significantly different between women and men (0.055 ± 0.006% vs 0.069 ± 0.008% and 0.0013 ± 0.0003% vs 0.0018 ± 0.0004%, respectively). CONCLUSIONS: These results demonstrate no sex-difference in EPC number in middle-age adults. Therefore, it is unlikely that differences in EPC number contribute to the gender-related differences in the prevalence of cardiovascular events in this population.
- Published
- 2008
- Full Text
- View/download PDF
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