Benfotiamine counteracts glucose toxicity
effects on endothelial progenitor cell differentiation via Akt/FoxO
signaling.
Marchetti V, Menghini R, Rizza S,
Vivanti A,
Feccia T, Lauro D, Fukamizu A, Lauro R, Federici M.
Department of Internal Medicine
University of Rome Tor Vergata
Via Montpellier 1, 00133 Rome, Italy.
Diabetes. 2006 Aug;55(8):2231-7
Abstract
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.
