Sulodexide increases mRNA expression of glutathione-related genes in human umbilical endothelial cells exposed to oxygen-glucose deprivation

INTRODUCTION: Sulodexide (SDX), a heparinoid used to treat vascular diseases, exerts anti-ischemic properties. However, the underlying molecular mechanisms remain unclear. Induction of glutathione (GSH)-dependent genes protects against ischemia. Here, we investigated the effect of SDX on GSH-associated gene expression in human umbilical endothelial cells (HUVECs) using an in vitro ischemia model. METHODS: The transcriptional expression of GSH-related genes (GCLc, xCT, GS, GPx1 and GR) in HUVECs treated without/with SDX (0.5 LRU/ml) under oxygen-glucose deprivation (OGD) condition for 1–6 h was analyzed by real-time polymerase chain reaction. RESULTS: GCLc and xCT were strongly up-regulated by SDX in HUVECs in the first 2 h of OGD. GS and GPx1 mRNA expression levels were significantly increased during any time interval in ischemic HUVECs treated with SDX. Furthermore, incubation of HUVECs with SDX in OGD for 1–4 h resulted in enhanced expression of GR. CONCLUSIONS: Our studies provide the first evidence that SDX activates GSH-related genes in OGD-injured HUVECs.