3-4-dideoxyglucosone-3-ene and Hyperglycemia

Hyperglycaemia and glucose degradation products (GDPs) are closely associated with oxidative stress and inflammation in diabetic patients, a condition that leads to endothelial dysfunction and cardiovascular problems. We evaluated the effect of citrate and gluconate on glucose- and GDP-induced endothelial inflammation by measuring changes in viability, inflammation and function in primary human umbilical vein endothelial cells (HUVECs). The extent of apoptosis/necrosis was measured by flow cytometry and visualised with confocal microscopy by staining with annexin V or propidium iodide, respectively. Protein kinase C-βII (PKC-βII) activation was evaluated with Western blotting. Incubation with glucose (30 mM) and GDP (50 µM) significantly increased PKC-βII expression, endothelial cell death and inflammation. The addition of citrate decreased hyperglycaemia-induced apoptosis (p = 0.021), necrosis (p = 0.04) and reduced PKC-βII expression (p = 0.021) down to background levels. Citrate improved endothelial function by reducing the inflammatory markers (p = 0.01) and by decreasing neutrophil diapedesis (p = 0.012). These results suggest that citrate may have therapeutic potential by reducing hyperglycaemia-induced endothelial inflammation and abolishing endothelial dysfunction.

Topics: Anti-Inflammatory Agents; Apoptosis; Blotting, Western; Cell Survival; Cells, Cultured; Citric Acid; Coculture Techniques; Enzyme Activation; Flow Cytometry; Gluconates; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Inflammation; Intercellular Adhesion Molecule-1; Microscopy, Confocal; Necrosis; Neutrophils; Protein Kinase C; Protein Kinase C beta; Pyrones; Transendothelial and Transepithelial Migration