Preventing arteries becoming hardened in diabetes

Investigating the role of RANKL signalling and glycation in vascular calcification and the potential for anti-calcification strategies 

It is estimated that by 2030, nearly 552 million people will have diabetes in the UK. Understanding new ways to treat complications associated with diabetes will make a difference to people living with the condition. Blood vessels are made up of smooth muscle cells (SMCs) which normally contract and expand to enable the blood to flow around the body. In coronary heart disease and diabetes, some of these vessels can get blocked by the build-up of fatty substances in the blood vessel wall. In diabetes, the SMCs can become hardened and calcified like bone. Currently, little is known about the calcification process, and there is no known treatment or cure. The BHF has now awarded a grant to Professor M Yvonne Alexander and colleagues to understand this process in diabetes. We know that in diabetes, proteins in the blood and in blood vessels react with sugars to form molecules called advanced glycation end-products (AGEs), and these can alter a chemical signalling pathway called RANKL/OPG. The team will investigate these molecules in more detail to work out if they influence how cells behave and if they are responsible for blood vessels becoming calcified. They will find out if we can block these pathways with a new drug to prevent the cells hardening and if some patients are more prone to calcification than others. This research will help us understand why blood vessels become calcified in diabetes and may reveal a new way to prevent or treat it.