https://scholars.lib.ntu.edu.tw/handle/123456789/468546
Title: | High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms | Authors: | Chen Y.-H. Lin S.-J. Lin F.-Y. Wu T.-C. Tsao C.-R. Huang P.-H. Liu P.-L. YUH-LIEN CHEN Chen J.-W. |
Issue Date: | 2007 | Journal Volume: | 56 | Journal Issue: | 6 | Start page/Pages: | 1559-1568 | Source: | Diabetes | Abstract: | OBJECTIVE - Endothelial progenitor cells (EPCs) are impaired in diabetes. This study aimed to investigate the direct effects of high glucose on EPCs. RESEARCH DESIGN AND METHODS - Mononuclear cells isolated from healthy subjects were incubated with glucose/mannitol or drugs for EPC study. After 4 days of culture, attached early EPCs appeared. The monolayer late EPCs with cobblestone shape appeared at 2-4 weeks. Various immunofluroscence stainings were used to characterize the early and late EPCs. Senescence assay and the activity of endothelial nitric oxide synthase (eNOS) were determined. Migration and tube formation assay were done to evaluate the capacity for vasculogenesis in late EPCs. RESULTS - Chronic incubation with high glucose but not mannitol (osmotic control) dose-dependently reduced the number and proliferation of early and late EPCs, respectively. High glucose enhanced EPC senescence and impaired the migration and tube formation of late EPCs. High glucose also decreased eNOS, FoxO1, and Akt phosphorylation and bioavailable nitric oxide (NO) in both EPCs. The effects of high glucose could be ameliorated by coincubation with NO donor sodium nitroprusside or p38 mitogen-activated protein kinase inhibitor and deteriorated by eNOS inhibitor or PI3K (phosphatidylinositol 3′-kinase) inhibitor. Antioxidants including vitamin C, N-acetylcysteine - and polyethylene glycol (PEG)-conjugated superoxide dismutase, and PEG-catalase had no effects, whereas pyrrolidine dithiocarbamate, diphenyleneiodonium, apocynin, and rotenone even deteriorated the downregulation of both EPCs. CONCLUSIONS - High glucose impaired the proliferation and function of early and late EPCs. NO donor but not antioxidants reversed the impairments, suggesting the role of NO-related rather than oxidative stress-mediated mechanisms in hyperglycemia-caused EPC downregulation. ? 2007 by the American Diabetes Association. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34249696575&doi=10.2337%2fdb06-1103&partnerID=40&md5=b5089c9210dc3cc726c436d970b013c7 https://scholars.lib.ntu.edu.tw/handle/123456789/468546 |
ISSN: | 0012-1797 | DOI: | 10.2337/db06-1103 | SDG/Keyword: | acetylcysteine; apocynin; ascorbic acid; diphenyliodonium salt; endothelial nitric oxide synthase; glucose; macrogol; nitric oxide; nitroprusside sodium; phosphatidylinositol 3 kinase inhibitor; protein kinase B; pyrrolidine dithiocarbamate; rotenone; superoxide dismutase; transcription factor FKHR; angiogenesis; article; bioavailability; cell count; cell isolation; cell level; cell migration; cell proliferation; controlled study; dose response; down regulation; endothelium cell; enzyme activity; enzyme phosphorylation; human; human cell; human cell culture; immunofluorescence; immunohistochemistry; mononuclear cell; osmotic potential; oxidative stress; priority journal; senescence; stem cell; Adult; Cell Aging; Cell Division; Cell Movement; Cell Separation; Colony-Forming Units Assay; Endothelium, Vascular; Glucose; Humans; Kinetics; Leukocytes, Mononuclear; Mannitol; Neovascularization, Physiologic; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Stem Cells |
Appears in Collections: | 解剖學暨細胞生物學科所 |
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