Effects of a novel selenosugar on primary human vascular cells, mouse aortic rings and atherosclerosis in apoE-/- mice

Atherosclerosis is characterized by chronic low-grade inflammation, large numbers of activated leukocytes, and the deposition of cholesterol and lipids in the artery wall. This project has investigated a novel seleno-sugar (1,4-anhydro-4-seleno-D-talitol, SeTal) as a potential regulator of oxidative stress, inflammation and atherosclerosis. SeTal did not affect the viability of human coronary artery endothelial and smooth muscle cells at low mM concentrations, or modulate thioredoxin reductase 1 or glutathione peroxidase 1 activity or levels. Concurrent or pre-treatment of cells with SeTal protected against toxicity induced by H 2 O 2 or HOCl. Studies on murine aortic rings showed that high concentrations of SeTal alone induced aortic relaxation on long-term treatment, and preserved endothelial cell-dependent relaxation on exposure to 50 µM HOCl. Oral dosing with SeTal (via drinking water) of apoE-/- mice did not affect weight gain, water consumption, or animal welfare. Intact SeTal was detected in plasma, liver and kidneys at micromolar levels. Plasma total cholesterol, triglycerides, and the inflammatory markers MCP-1, IL-6 and SAA were unaffected. The effects of SeTal on arterial atherosclerotic plaque size and composition will be presented.