MRC funded project - Control of collateral formation in cardiovascular disease by VEGF

Diabetics have increased risk of cardiovascular disease. In non-diabetic patients, when blood vessels block, the body generates new vessels circumventing the blockage, but this collateral growth is less common in diabetics. Blood vessel growth, (angiogenesis), occurs in response to vascular endothelial growth factor (VEGF), generated in white blood cells that home to tissue with poor blood supply.

VEGF can be made in multiple types, some of which stimulate angiogenesis and others that prevent it. Using mouse models, we discovered that one of the reasons why collaterals do not form as well in diabetes is that the type of VEGF made in diabetic patients is anti-angiogenic. We also confirmed that in humans, this anti-angiogenic VEGF is found more in diabetic than non-diabetic patients. Anti-angiogenic VEGF expression is stimulated by a circulating protein called Wnt5a.

This project will find out whether human diabetics have the same control of collateral formation by Wnt5a, and how Wnt5a causes the cells to make the anti-angiogenic form of VEGF. If we can pinpoint this mechanism then we will try and change the production of VEGF so that blood vessels can grow again in diabetic mice. This could lead to new treatments for cardiovascular disease in diabetics.

For more details on the lab, go to http://www.tvbl-nottingham.org/studentships.html