The human aorta stiffens with age but this is not a benign process with a stiffer aorta conferring a higher risk of cardiovascular events including stroke. Recent work by Dr Yasmin from the Division of Experimental Medicine & Immunotherapeutics, Department of Medicine (O’Shaughnessy and Wilkinson groups) published in Scientific Reports has identified two extracellular matrix proteins (aggrecan and fibulin-1) which have a key role in aortic stiffening. Aggrecan is an essential component of the ‘shock-absorbing’ cartilage in joints, and the team discovered that similar to joint cartilage these proteins in the aorta degrade with age (see figure).
Using a combination of genetic, proteomic and biomechanical techniques, they found that aggrecan, in stiff aortas specifically, lost chondroitin-sulphate binding domains, which are necessary for maintaining aortic elasticity. Currently several drugs are being developed to prevent degradation of aggrecan in joints, and this raises the possibility that these therapeutic agents may one day be used to slow or even reverse the ‘molecular-aging’ process of arterial stiffening.