Based on the novel findings in this study we propose the following hypothetical disease mechanism to explain EC-mediated cardiovascular pathology in HGPS (Figure 7D): Progerin induces persistent mechanical stress leading to the activation of the p53 pathway, and its target miRs, such as miR34-5p, rise particularly at mechanosensitive atheroprone vessel bifurcations. Here, LMNA is linked to Hutchinson-Gilford progeria syndrome.