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oai:repisalud.isciii.es:20.500.12105/258412025-12-18T13:00:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Benedicto, Ignacio author Hamczyk, Magda R author Nevado, Rosa M author Barettino, Ana author Carmona, Rosa M author Espinós-Estévez, Carla author Gonzalo, Pilar author de la Fuente-Pérez, Miguel author Andrés-Manzano, María J author González-Gómez, Cristina author Dorado, Beatriz author Andrés, Vicente author 2024-10-31 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. Aging Cell. 2024 Oct 31:e14389. Aging Cell 39479939 https://hdl.handle.net/20.500.12105/25841 Hutchinson‐Gilford progeria syndrome atherosclerosis cardiovascular disease endothelial cells progerin Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death.