2026-05-23T14:00:34Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/191932024-09-27T07:56:58Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Benedicto, Ignacio author Carmona, Rosa M author Barettino, Ana author Espinós-Estévez, Carla author Gonzalo, Pilar author Nevado, Rosa M author de la Fuente-Pérez, Miguel author Andres-Manzano, Maria J. author Gonzalez-Gomez, Cristina author Rolas, Loïc author Dorado, Beatriz author Nourshargh, Sussan author Hamczyk, Magda R. author Andres, Vicente author 2024-04-30 Hutchinson-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. Proc Natl Acad Sci USA. 2024 Apr 30;121(18):e2400752121. 10.1073/pnas.2400752121 1091-6490 Proceedings of the National Academy of Sciences of the United States of America 38648484 http://hdl.handle.net/20.500.12105/19193 Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells.