Monitoring and recovery of hyperglycaemia-induced endothelial dysfunction with rheopheresis in diabetic lower extremity ulceration with hyperviscosity.

AIMS: Rheopheresis is an extracorporeal haematotherapy that improves haemorheological status by filtering proteins that enhance blood viscosity. It also has anti-inflammatory effects by removing inflammatory cytokines. Our study aims to examine the effects of rheopheresis on the endothelial status in diabetic lower extremity ulceration. METHODS: In vitro experiments were performed in a HUVEC model to mimic hyperglycaemic stress. We determined the changes in gene expression levels of IL-6, IL-8, TNF-alpha, endothelin convertase enzyme, ET-1, and NO synthase, as well as the ROS and intracellular GSH levels upon hyperglycaemia. In in vivo studies, two rheopheresis procedures were performed on seven patients with diabetic lower extremity ulceration with hyperviscosity, and we measured the changes in plasma concentrations of ET-1, TXB2, SOD enzyme activity, and extracellular components of the glutathione pool depending on treatments. RESULTS: Our results showed that hyperglycaemia increases endothelial expression of inflammatory cytokines, ET-1, and endothelin convertase enzyme, while NO synthase was decreased. As a result of rheopheresis, we observed decreased ET-1 and TXB2 concentrations in the plasma and beneficial changes in the parameters of the glutathione pool. CONCLUSION: To summarize our results, hyperglycaemia-induced oxidative stress and endothelial inflammation can be moderated by rheopheresis in diabetic lower extremity ulceration with hyperviscosity.

Anthocyanin-Rich Sour Cherry Extract Attenuates the Lipopolysaccharide-Induced Endothelial Inflammatory Response.

The anthocyanin content of Hungarian sour cherry is remarkable based on our preliminary investigations. Nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. The objective of this work was to investigate the the effect of purified sour cherry extract using human umbilical cord vein endothelial cells (HUVECs) as the inflammatory model. HUVECs were isolated by enzymatic digestion and characterized by flow cytometry. The optimal concentration range of sour cherry extract was selected based on MTT, apoptosis, and necrosis assays. Cells were divided into three groups, incubating with M199 medium as control, or with lipopolysaccharide (LPS) or with LPS plus anthocyanin extract (ACE). The effect of sour cherry extract on oxidative stress, pro-inflammatory factors, and arachidonic pathway was investigated. An amount of 50 µg/mL ACE (ACE50) was able to increase the level of glutathione and decrease the ROS, thereby improving the unbalanced redox status in inflammation. ACE50 lowered pro-inflammatory cytokine levels including Interleukin-6 (IL-6), regulated on activation, normal T cell expressed and secreted (RANTES), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-α). ACE50 affected the arachidonic acid pathway by reducing the LPS-induced enzyme expression (cyclooxygenase-1, cyclooxygenase-2, and prostacyclin synthase). The extract under investigation seems to have a pleiotropic effect including anti-oxidative, anti-inflammatory, hemostatic, and vasoactive effects. Our results indicate that purified sour cherry extract could reduce the LPS-induced inflammatory response, thereby improving endothelial dysfunction.