Uncovering how blocking BACE1 protects blood vessels in type 2 diabetes

What are the mechanisms involved in the beneficial effects of BACE1 inhibition on endothelial function in type 2 diabetes?

Circulatory diseases – those that affect our veins and arteries – are caused by damage to endothelial cells, which line our blood vessels. Among other effects, this damage stops vessels responding to signals that should keep blood pressure normal. In people with diabetes this damage happens faster, raising the risk of heart attacks, causing leg ulcers and other problems. There is currently no effective treatment to prevent these effects of diabetes on the endothelium. In Leeds, Dr Meakin has discovered that a protein called ß-site APP-cleaving enzyme 1 (BACE1) is involved in this process. He’s shown that mice that have been genetically engineered to lack BACE1 are protected from endothelial damage, and that diabetes increases BACE1 levels in blood vessels. He believes that BACE1 could control the release of some important substances that help vessels respond normally and therefore may have an important role in causing vascular disease in people with diabetes. In this study involving mice, Dr Meakin will try and work out how BACE1 does this. His hope is that drugs that stop BACE1 working could help to keep blood vessels healthy in people with diabetes, protecting against heart attacks and other vascular diseases.