Understanding the role of proteoglycans in the elasticity of the heart

An ultrastructural study to elucidate how proteoglycans determine the elastic properties of the cardiac extracellular matrix in health and disease

The pumping action of the heart is performed by the beating of muscle cells called cardiac myocytes. These are embedded in a type of ‘biological scaffold’ known as the extracellular matrix (ECM), which organises the myocytes to allow efficient and coordinated pumping of blood by the heart. One of the ECM’s properties is its elasticity. If this is altered, the work of the cardiac myocytes becomes less efficient and in extreme cases this can lead to heart failure. Collagen is an important component that gives the ECM its elasticity, and the amount of collagen is controlled by a group of molecules called proteoglycans. Surprisingly, given their important role, little is known about the role of proteoglycans in the heart compared with other parts of the body. In this fellowship, Dr Christian Pinali is using methods he’s developed for studying proteoglycans in the eye and applying them to the heart. He hopes to work out exactly how proteoglycans guide the arrangement of collagen fibres. He’s also interested in how this process goes wrong – and whether proteoglycans play a role in the build-up of scar tissue in the heart. This will provide important insights into a process called fibrosis – the laying down of scar tissue after damage – which ultimately leads to heart failure.