Dose-Dependent Effects of Allopurinol on Human Foreskin Fibroblast Cells and Human Umbilical Vein Endothelial Cells under Hypoxia

作者：Sun Yu; George Jacob^*; Rocha Sonia

来源：PLos One, 2015, 10(4): UNSP e0123649.

DOI：10.1371/journal.pone.0123649

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1 alpha protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1 alpha mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells.

• 出版日期2015-4-1