Thiamine pyrophosphate diminishes nitric oxide synthesis in endothelial cells.

Abstract

Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n=20), were incubated with 5, 15 or 30mmol/L glucose, in absence or presence of 0.625mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P<0.05), and cell viability (> 90%; P<0.001) after 48h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24h (> 7%; P<0.001) and 48h (> 10%; P<0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48h (P<0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24h (< 171 pmol/μg protein; P<0.001), and 48h (< 250 pmol/μg protein; P<0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.