A sugar coated solution to stop blood vessel leakiness

The differential modification of glycosaminoglycans by VEGFA and VEGFC and consequential effects on GEnC barrier integrity

Cells that line the blood vessels (endothelial cells) are coated with a protective layer of sugars, called the glycocalyx, which helps the blood vessels to function normally. In health, vascular endothelial growth factor-A (VEGFA) is an important protein that promotes new blood vessel growth, maintains fluid exchange between the blood and the surrounding tissue and stops proteins from leaking out of the blood. But when VEGFA becomes over active, it can make blood vessels leaky to fluid and proteins, possibly by removing the glycocalyx. Blood vessel leakiness is a problem in conditions like cancer, inflammation, blindness and in kidney disease, but blocking VEGFA completely to prevent leakiness causes side effects. To understand better how to control blood vessel leakiness, a good model to use is the glomerulus in the kidney. This is a tightly regulated network of tiny vessels where leakiness is marked by larger proteins passing into the urine. VEGFA is produced locally within the glomerulus as is VEGFC, another related growth factor, which has many similar effects on blood vessels as VEGFA, but importantly VEGFC makes glomerular endothelial cell layers less leaky and seems to preserve the protective barrier. This studentship will study how VEGFs modify the glycocalyx in the glomerulus, whether this affects the leakiness of the glomerulus and whether VEGFC can protect against the VEGFA-associated glycocalyx changes. The research could lead to new treatments for blood vessel leakiness in the future.