Benedicto, IgnacioCarmona, Rosa MBarettino, AnaEspinós-Estévez, CarlaGonzalo, PilarNevado, Rosa Mde la Fuente-Pérez, MiguelAndres-Manzano, Maria J.Gonzalez-Gomez, CristinaRolas, LoïcDorado, BeatrizNourshargh, SussanHamczyk, Magda R.Andres, Vicente2024-04-242024-04-242024-04-30Proc Natl Acad Sci USA. 2024 Apr 30;121(18):e2400752121.http://hdl.handle.net/20.500.12105/19193Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin-induced atherosclerosis is prevented in HGPSrev-Cdh5-CreERT2 and HGPSrev-SM22α-Cre mice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. HGPSrev-Cdh5-CreERT2 mice were undistinguishable from HGPSrev mice with ubiquitous progerin expression, in contrast with the ameliorated progeroid phenotype of HGPSrev-SM22α-Cre mice. To study atherosclerosis, we generated atheroprone mouse models by overexpressing a PCSK9 gain-of-function mutant. While HGPSrev-Cdh5-CreERT2 and HGPSrev mice developed a similar level of excessive atherosclerosis, plaque development in HGPSrev-SM22α-Cre mice was reduced to wild-type levels. Our studies demonstrate that progerin suppression in VSMCs, but not in ECs, prevents exacerbated atherosclerosis in progeroid mice.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacional3864848412118e240075212110.1073/pnas.24007521211091-6490Proceedings of the National Academy of Sciences of the United States of Americaopen access