Does RAGE cause leaky blood vessels?

RAGE-activated endothelial barrier dysfunction: a possible link to glycocalyx and Robo4 disruption

After heart surgery, some patients can develop a condition called the systemic inflammatory response syndrome (SIRS). When SIRS occurs, blood vessels become leaky and fluid can accumulate in the heart, lungs and other organs which prevents them from working properly. As a result, patients often have to stay longer in the hospital intensive care unit which can affect their long-term health. The aim of this PhD studentship, based at Imperial College London, is to work out what causes blood vessel leakiness, and how this could be prevented from happening. The student will investigate if a protein receptor called RAGE is involved in SIRS. The team proposes that factors released during SIRS could activate RAGE, which results in blood vessels become leaky; either because a protective layer (the glycocalyx) that coats the inside of blood vessels is damaged, or because a protein called Robo4 that normally prevents leakiness does not work properly. They will test this theory by studying the blood of patients who have had heart surgery and by activating RAGE in cultured cells in the laboratory to see its effects. Fluid accumulation that occurs in SIRS and also in other conditions, like septic shock, is difficult to treat and it is hoped that this work will lead to the development of new drug therapies to prevent blood vessel leakiness.