CYANIDIN-3-O-GLUCOSIDE PROTECTS HUMAN ENDOTHELIAL CELLS AGAINST HYPOXIA-INDUCED DAMAGE

Hypoxia is characterized by a decreased O2 tension within cells and occurs under several pathophysiological situations including ischemia, cancer and inflammation. Concomitantly with turning down oxygen requirements, hypoxia also triggers mechanisms implicating an increased need of O2 by activating HIF-1 transcription factor. An excessive load of reactive oxygen species (ROS) generated under hypoxic conditions may result in cell injury and dysfunction. Exposure of endothelial cells (ECs) to hypoxia has been shown to induce either angiogenesis, associated with MMP2 and MMP9 metalloproteinase expression or death. Anthocyanins, a group of flavonoids present in several common vegetable foods, are under investigation for their chemopreventive activity. Antioxidant, anti-inflammatory and photoprotective activities have been reported for Cyanidin-3-glucoside (C3G), the main compound of this group. In the present study we have demonstrated that C3G pretreatment of human umbilical vein endothelial cells (HUVECs) is able to reduce the changes in cell redox status (intracellular GSH/GSSG ratio, cytosolic TAA and SOD activity) elicited by 48h of hypoxia. On this basis, we investigated a possible protective effect of C3G under the same experimental conditions on hypoxia-induced release/activation of metalloproteinases (MMPs). Our results indicate a time-dependent increase of hypoxia-mediated MMP expression starting at 24 h from the beginning of hypoxia, and further increasing 48 h. Cell pretreatment with C3G is associated with a significant dose-dependent decrease in MMP expression and release. Furthermore we demonstrated the involvement of HIF-1 transcription faction modulation by C3G in the observed effects. Our study suggests that C3G is able to prevent cellular redox status changes and MMP release/activation induced by hypoxic condition in EC.