The role of elastin-derived peptides in the progression of arterial stiffness and cardiovascular disease with a focus on autophagy inhibition as contributing mechanism.

Elastin is responsible for the elasticity of the vessel wall, but due to repetitive stretches and relaxations as we age, it will fracture, leading to arterial stiffness and the release of soluble elastin-derived peptides (EDPs). Some of these EDPs are biologically active and can play a role in the development of cardiovascular disease (CVD). Existing literature points towards a decline in autophagy by EDPs. Autophagy is a protective mechanism, that recycles damaged cell products into building blocks that are used to maintain cellular health. Lower autophagy levels can contribute to CVD. If EDPs can reduce autophagy, this might be an important mechanism by which they exert their detrimental effects. However, this has never been proven. Therefore, we would like to investigate whether EDPs can reduce autophagy and how this affects arterial stiffness and CVD. This will answer three research questions: (1) Can EDP signalling affect cellular function and lead to autophagy deficiency in vascular cells and monocytes? (2) What is the role of EDPs in the progression of arterial stiffness and is autophagy deficiency responsible for the observed effects? (3) Can EDP signalling enhance atherogenesis and is autophagy deficiency responsible for the observed effects? Overall, this research plan aims to better understand the role of EDPs in autophagy decline, vascular ageing and arterial stiffness in order to prevent or slow down this process and to improve quality of life.

Keywords:AUTOPHAGY, ARTERIAL STIFFNESS, EXTRACELLULAR MATRIX, AGEING

Disciplines:Vascular diseases, Cellular interactions and extracellular matrix