1. Endothelial cell‐specific progerin expression does not cause cardiovascular alterations and premature death.
- Author
-
Benedicto, Ignacio, Hamczyk, Magda R., Nevado, Rosa M., Barettino, Ana, Carmona, Rosa M., Espinós‐Estévez, Carla, Gonzalo, Pilar, Fuente‐Pérez, Miguel, Andrés‐Manzano, María J., González‐Gómez, Cristina, Dorado, Beatriz, and Andrés, Vicente
- Subjects
- *
PROGERIN , *VASCULAR smooth muscle , *CARDIOLOGICAL manifestations of general diseases , *HEART fibrosis , *NUCLEAR proteins - Abstract
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 (LmnaLCS/LCSCdh5‐CreERT2) and atheroprone mice (Apoe−/−LmnaLCS/LCSCdh5‐CreERT2) with EC‐specific progerin expression. Like progerin‐free controls, LmnaLCS/LCSCdh5‐CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone Apoe−/−LmnaLCS/LCSCdh5‐CreERT2 mice showed no alteration in body weight or lifespan versus Apoe−/−LmnaLCS/LCS 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF