Endothelial-to-mesenchymal transition contributes to accelerated atherosclerosis in Hutchinson–Gilford progeria syndrome

The main goal of this study was to gain insight into the mechanisms underlying phenotypic changes in endothelial cells during atherosclerosis associated with Hutchinson-Gilford progeria syndrome, a premature aging syndrome. To this end, we performed an RNAseq experiment with aortic intima samples from atheroprone mice with ubiquitous and VSMC-specific progeria expression and their corresponding controls. Aortic intima samples were collected from: Apoe-/-LmnaG609G/G609G mice (with ubiquitous progerin expression), Apoe-/-Lmna+/+ mice (with wild-type lamin A/C expression; controls for mice with ubiquitous progerin expression), Apoe-/-LmnaLCS/LCSSM22αCre (with VSMC-specific expression) and Apoe-/-LmnaLCS/LCS mice (with lamin C only expression; controls for mice with VSMC-specific expression). For each genotype 3-4 samples were prepared, each consisting of a pool of 12-14 mice. Following RNA sequencing, 3 comparisons were performed: between Apoe-/-LmnaG609G/G609G mice and Apoe-/-Lmna+/+ control mice, between Apoe-/-LmnaLCS/LCSSM22αCre mice and Apoe-/-LmnaLCS/LCS control mice and between Apoe-/-LmnaLCS/LCS control mice and Apoe-/-Lmna+/+ control mice.