Can targeting Porcupine prevent vein graft failure?

Attenuation of intimal thickening via porcupine inhibition

In coronary heart disease, fatty deposits in our blood vessels build up over time and restrict the flow of the blood to the heart. This can be treated using bypass vein grafting – where a piece of vein from the leg is used to bypass blockages and restore blood flow. However, this treatment doesn’t always work for long because the grafted vein wall can become thickened, narrowing the new vein. Professor George is working on a way to prevent this. Her lab has shown that a molecules called Wnts are important in causing thickening of the grafted vein. Specifically, they found that the molecule Wnt4 causes blood vessel cells to increase in number, and a second molecule, Wnt2, causes them to move. Both are crucial processes in the thickening of vein walls. Wnt2 and Wnt4 are regulated by another molecule called Porcupine, which controls the release of Wnt from the cells. In this project, Professor George will test whether blocking Porcupine can prevent vein narrowing in mice and human veins, and will determine how this happens. The results could identify whether Porcupine-blocking drugs can prevent vein graft failure in people with heart disease.