Thiamine reverses hyperglycemia-induced dysfunction in cultured endothelial cells.
BACKGROUND
High levels of glucose have previously been shown to inhibit endothelial cell migration and increase secretion of the von Willebrand factor (vWF), a marker of endothelial cell damage. This study investigates whether thiamine, an important coenzyme in intracellular glucose metabolism, improves endothelial cell migration and decreases von Willebrand factor secretion under hyperglycemic conditions.


METHODS
Bovine aortic endothelial cells (BAECs) were grown under physiological glucose (5.5 mmol/L) and hyperglycemic (13.8 mmol/L and 27.7 mmol/L) conditions with or without thiamine (200 micromol/L) supplementation. Endothelial cell migration was investigated in monolayers of BAECs that were wounded by scraping. The distance of migration, the number of migrating cells, and the surface area covered by the migrating cells were measured. Secretion of vWF by BAECs under physiological glucose and high glucose conditions with or without thiamine (200 micromol/L) supplementation was studied with enzyme-linked immunosorbent assay.


RESULTS
Under hyperglycemic conditions, there was a significant decrease in the number of endothelial cells and an increase in the secretion of vWF (P <.001). Thiamine treatment limited this inhibitory effect of elevated glucose levels on BAECs. Glucose (27.7 mmol/L) significantly decreased the migration distance of BAECs into the wounded area to 4.0 +/- 1.4 cm, as compared with 6.2 +/- 0.3 cm in the control. Thiamine supplementation restored the migration distance by BAECs (6.94 +/- 0.7 cm) and the wound surface area covered (47.7 +/- 5.6 cm(2)) (P <.001).


CONCLUSIONS
Hyperglycemia activates BAECs and promotes secretion of vWF, a marker of endothelial cell damage. Thiamine inhibits this endothelial cell activation and the effects of hyperglycemia on endothelial cell migration. This beneficial effect of thiamine limiting endothelial cell dysfunction is possibly through the diversion of glucose flux from anaerobic to aerobic pathways. The data from this study lead to the speculation that thiamine intake may mitigate or delay vascular complications of diabetes.
Ascher
E
E
Division of Vascular Surgery, Maimonides Medical Center, Brooklyn, NY 11219, USA.
Gade
P V
PV
Hingorani
A
A
Puthukkeril
S
S
Kallakuri
S
S
Scheinman
M
M
Jacob
T
T
D000818:Animals; D002417:Cattle; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000209:etiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000633:toxicity*; D013831:Thiamine / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D005947:Glucose; D013831:Thiamine