Central factors that increase arterial stiffness across the lifespan are endothelial dysfunction, a reduced elastin-to-collagen ratio and proliferation, and phenotypic switching of VSMCs.65 Biomechanical analysis of animal models has indicated that up to 50% of age-associated arterial stiffness is due to VSMCs.66 An overview of the underlying mechanisms can be found in previous reviews.14,27,33,65,67–70. Here, ELN is linked to endothelial dysfunction.