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.

Marchetti, V., Menghini, R., Rizza, S., Vivanti, A., Feccia, T., Lauro, D., et al. (2006). Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling. DIABETES, 55(8), 2231-2237 [10.2337/db06-0369].

Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling

MENGHINI, ROSSELLA;RIZZA, STEFANO;LAURO, DAVIDE;LAURO, RENATO;FEDERICI, MASSIMO
2006-08-01

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.
ago-2006
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - MEDICINA INTERNA
Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITA' MOTORIE
Settore MED/50 - SCIENZE TECNICHE MEDICHE APPLICATE
Settore MED/13 - ENDOCRINOLOGIA
Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
Settore MED/49 - SCIENZE TECNICHE DIETETICHE APPLICATE
English
Con Impact Factor ISI
Androstadienes; Forkhead Transcription Factors; Humans; Glucose; Thiamine; Cell Differentiation; Proto-Oncogene Proteins c-akt; Endothelial Cells; Protein Kinase Inhibitors; Cells, Cultured; Stem Cells; Signal Transduction; Cell Division
NITRIC-OXIDE SYNTHASE; VASCULAR COMPLICATIONS; DIABETES-MELLITUS; ANGIOGENESIS; TRANSCRIPTION; MICE; DYSFUNCTION; METABOLISM; MECHANISM; THIAMINE
Marchetti, V., Menghini, R., Rizza, S., Vivanti, A., Feccia, T., Lauro, D., et al. (2006). Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling. DIABETES, 55(8), 2231-2237 [10.2337/db06-0369].
Marchetti, V; Menghini, R; Rizza, S; Vivanti, A; Feccia, T; Lauro, D; Fukamizu, A; Lauro, R; Federici, M
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/40819
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