Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the dev...

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Detalles Bibliográficos
Autores: Benedicto, Ignacio, Hamczyk, Magda R, Nevado, Rosa M, Barettino, Ana, Carmona, Rosa M, Espinós-Estévez, Carla, Gonzalo, Pilar, de la Fuente-Pérez, Miguel, Andrés-Manzano, María J, González-Gómez, Cristina, Dorado, Beatriz, Andrés, Vicente
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25841
Acceso en línea:https://hdl.handle.net/20.500.12105/25841
Access Level:acceso abierto
Palabra clave:Hutchinson‐Gilford progeria syndrome
atherosclerosis
cardiovascular disease
endothelial cells
progerin
Descripción
Sumario:Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS. To tackle this question, we generated atherosclerosis-free mice (LmnaCdh5-CreERT2) and atheroprone mice (ApoeLmnaCdh5-CreERT2) with EC-specific progerin expression. Like progerin-free controls, LmnaCdh5-CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone ApoeLmnaCdh5-CreERT2 mice showed no alteration in body weight or lifespan versus ApoeLmna controls and did not develop vascular alterations or aggravated atherosclerosis. Our results indicate that progerin expression in ECs is not sufficient to cause the cardiovascular phenotype and premature death associated with progeria.

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