Abstract
Objective:
Function and availability of circulating progenitor cells (CPC) have been shown to be impaired in patients with diabetes mellitus (DM). Therefore, the aim of the present study was to analyze possible mechanisms leading to the reduction of CPC amount and function.
Methods and results:
Peripheral blood mononuclear cells (MNCs) of healthy donors (n=15) were cultivated under hyperglycemia (HG) conditions (12 mmol/L D-Glucose) or in osmotic control medium (Con) (5 mmol/L D-Glucose plus 7 mmol/L L-Glucose) for 7 days. CPC amount was determined by uptake of acetylated low-density lipoprotein and lectin binding. On the functional level, cell cycle status, nitric oxide (NO) production, and migrational and integrative capacity of CPCs were assessed. HG conditions caused a significant decrease in CPC amount derived from healthy MNCs. Furthermore, HG conditions led to a functional impairment, reflected in a decreased NO production and matrix metalloproteinase (MMP)-9 activity, as well as an impairment of the migrational and integrative capacities.
Conclusions:
HG, a main feature of DM, affects important functional characteristics of CPCs. These results may provide further insight into the pathomechanism of endothelial dysfunction in HG.
MeSH terms
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Adolescent
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Adult
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Apoptosis
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Cell Cycle Proteins / genetics
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Cell Survival
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p21
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Diabetes Complications / pathology
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Diabetes Complications / physiopathology
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Female
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Glucose / pharmacology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / physiology*
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Humans
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Hyperglycemia / pathology*
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Hyperglycemia / physiopathology*
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / drug effects
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Male
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Middle Aged
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type III
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Phosphoprotein Phosphatases / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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RNA, Messenger / analysis
Substances
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Proto-Oncogene Proteins
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RNA, Messenger
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Nitric Oxide
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NOS3 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type III
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Phosphoprotein Phosphatases
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Matrix Metalloproteinase 9
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Glucose