Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells.
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.


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.
Kränkel
Nicolle
N
Department of Internal Medicine/Cardiology, Heart Center Leipzig, University of Leipzig, Germany.
Adams
Volker
V
Linke
Axel
A
Gielen
Stephan
S
Erbs
Sandra
S
Lenk
Karsten
K
Schuler
Gerhard
G
Hambrecht
Rainer
R
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology* / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000032:analysis
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; D020780:Matrix Metalloproteinase 9; D005947:Glucose