In common with most dynamic tissues, the mechanical properties of arteries are determined by the relative composition and architecture of key structural extracellular matrix (ECM) proteins including fibrillar collagens and elastic fiber components. Although it is apparent that age-related loss of ECM homeostasis leads to arteriosclerosis (vascular stiffening), which in turn is associated with the development of both fatal strokes and heart failure, the causative mechanisms and principal molecular targets remain poorly defined.

Whilst there are many potential effectors of ECM degradation it is unclear how these mechanisms could drive selective molecular remodelling in the aging vasculature. Our data suggest that the preferential oxidation of cysteine-rich elastic fibre-associated components may play a key role in initiating and promoting tissue remodeling (and hence stiffening) in aging mammals. In complementary studies we are developing new micro-mechanical methodologies, which in combination with conventional histological approaches, are capable of localising arteriosclerotic changes to specific regions and hence molecular targets in aging and diabetic vessels.