Thiamine reverses hyperglycemia-induced dysfunction in cultured endothelial cells

Background. High levels of glucose have previously been shown to inhibit en dothelial cell migration and increase secretion of the von Willebrand facto r (vWF), a marker of endothelial cell damage. This study investigates wheth er thiamine, an important coenzyme in intracellular glucose metabolism, imp roves endothelial cell migration and decreases von Willebrand factor secret ion under hyperglycemic conditions. Methods. Bovine aortic endothelial cells (BAECs) were grown under physiolog ical glucose (5.5 mmol/L) and hyperglycemic (13.8 mmol/L and 27.7 mmol/L) c onditions with or without thiamine (200 mu mol/L) supplementation. Endothel ial cell migration was investigated in monolayers of BAECs that were wounde d by scraping. The distance of migration, the number of migrating cells, an d the surface area covered by the migrating cells were measured. Secretion of vWF by BAECs tinder physiological glucose and high glucose conditions wi th or without thiamine (200 mu mol/L) supplementation was studied with enzy me-linked immunosorbent assay. Results. Under hyperglycemic conditions, there was a significant decrease i n the number of endothelial cells and an increase in the secretion of vWF ( P < .001). Thiamine treatment limited this inhibitory effect of elevated gl ucose levels on BAECs. Glucose (27.7 mmol/L) significantly decreased the mi gration distance of BAECs into the wounded area to 4.0 +/- 1.4 cm, as compa red with 6.2 +/- 0.3 cm in the control. Thiamine supplementation restored t he 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 i s possibly through the diversion of glucose flux from anaerobic to aerobic pathways. The data from this study lead to the speculation that thiamine in take may mitigate or delay vascular complications of diabetes.