Elastic fibers are mainly composed of elastin, which represents -with collagen- the main structural matrix component of the vascular wall. During vascular ageing, elastin degradation generates bioactive elastin-derived peptides (EDPs), which can play a role in the development of many age-related vascular pathologies. Most of the biological effects induced by these PDEs involve the elastin receptor complex (ERC), and particularly its catalytic subunit neuraminidase-1 (NEU-1). Indeed, our team has notably shown that PDEs, after binding to CRE and activation of NEU-1, play a key role in the development of atherosclerosis. The aim of this thesis project will consist in developping an inhibition strategy targeting NEU-1 (using cell biology and biochemistry approaches) in the context of atherosclerosis. The objective of this project will consist in evaluating the ability of a combination of two interfering peptides to inhibit NEU-1 dimerization/activation and to reduce atherosclerotic plaque progression in mouse models of atherosclerosis.
Keywords : Neuraminidase-1, Atherosclerosis, Interfering peptides, Membrane proteins