Peripheral artery disease (PAD) is the third most common form of atherosclerotic disease resulting in gangrene and requiring amputation of limbs. There is no cure, with treatment focusing on lifestyle changes and managing of risk factors. Importantly, females have worse outcomes than men. The reasons for this are unclear. The endothelium is a critical organ for cardiovascular homeostasis, controlling vessel tone and constriction, inflammation, platelet adhesion and thrombosis, and generating new blood vessels for repair after injury (angiogenesis). Endothelial dysfunction may contribute to sex-dependent changes in PAD. This project seeks to examine the sex-dependent changes in PAD pathophysiology using vivo models and assess the behaviour of endothelial cells under low oxygen and diabetic conditions in vitro.