Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19193
Título
Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells.
Autor(es)
Benedicto, Ignacio CNIC | Carmona, Rosa M CNIC | Barettino, Ana CNIC | Espinós-Estévez, Carla | Gonzalo, Pilar CNIC | Nevado, Rosa M CNIC | de la Fuente-Pérez, Miguel | Andres-Manzano, Maria J. CNIC | Gonzalez-Gomez, Cristina CNIC | Rolas, Loïc | Dorado, Beatriz CNIC | Nourshargh, Sussan | Hamczyk, Magda R. CNIC | Andres, Vicente CNIC
Fecha de publicación
2024-04-30
Cita
Proc Natl Acad Sci USA. 2024 Apr 30;121(18):e2400752121.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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- Exacerbated atherosclerosis in ...
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