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Benfotiamine Counteracts Glucose Toxicity Effects on Endothelial Progenitor Cell Differentiation via Akt/FoxO Signaling
Author(s) -
Valentina Marchetti,
Rossella Menghini,
Stefano Rizza,
Alessia Vivanti,
Tiziana Feccia,
Davide Lauro,
Akiyoshi Fukamizu,
Renato Lauro,
Massimo Federici
Publication year - 2006
Publication title -
diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.219
H-Index - 330
eISSN - 1939-327X
pISSN - 0012-1797
DOI - 10.2337/db06-0369
Subject(s) - progenitor cell , protein kinase b , endothelial progenitor cell , chemistry , microbiology and biotechnology , pharmacology , endothelial stem cell , toxicity , signal transduction , cancer research , biology , biochemistry , stem cell , in vitro , organic chemistry
Dysfunction of mature endothelial cells is thought to play a major role in both micro- and macrovascular complications of diabetes. However, recent advances in biology of endothelial progenitor cells (EPCs) have highlighted their involvement in diabetes complications. To determine the effect of glucotoxicity on EPCs, human EPCs have been isolated from peripheral blood mononuclear cells of healthy donors and cultured in the presence or absence of high glucose (33 mmol/l) or high glucose plus benfotiamine to scavenge glucotoxicity. Morphological analysis revealed that high glucose significantly affected the number of endothelial cell colony forming units, uptake and binding of acLDL and Lectin-1, and the ability to differentiate into CD31- and vascular endothelial growth factor receptor 2-positive cells. Functional analysis outlined a reduced EPC involvement in de novo tube formation, when cocultured with mature endothelial cells (human umbilical vein endothelial cells) on matrigel. To explain the observed phenotypes, we have investigated the signal transduction pathways known to be involved in EPC growth and differentiation. Our results indicate that hyperglycemia impairs EPC differentiation and that the process can be restored by benfotiamine administration, via the modulation of Akt/FoxO1 activity.

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