Uncovering a new target for medicines that could treat heart failure

Identification of the constitutive, secretory-pathway, endothelin-converting enzyme

Endothelin-1 is a chemical compound that can cause blood vessels to constrict. This can lead to high blood pressure and worsen the symptoms of heart failure, a debilitating condition where the heart is unable to meet the body’s demands. Heart failure patients who have high blood levels of endothelin-1 have a greater risk of dying. Clinical trials of endothelin blockers in heart failure patients initially gave promising results, but frequent side effects made them unsuitable as a treatment. Now, Professor Corder is investigating a new avenue for controlling endothelin-1. Another approach to reducing levels of endothelin-1 is to reduce how much of it is made in the body. Endothelin-converting enzymes (ECE) are crucial to its synthesis and are therefore a key target. However, efforts to target one of these enzymes, called ECE-1, have failed to produce a new therapy. Professor Corder believes that another member of the ECE family, called spECE, may be a more effective target. Using human blood vessel cells grown in the laboratory, Professor Corder hopes to prove that spECE is essential for synthesis of endothelin-1 in such cells. He also aims to find out if this enzyme is important for the production of endothelin-1 in other cell types. This could be the first step that leads to a drug that inhibits spECE, lowers endothelin-1 and ultimately improve heart failure symptoms.