Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16840
Título
Atherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation.
Autor(es)
Martinez-Campanario, M C | Cortés, Marlies | Moreno-Lanceta, Alazne | Han, Lu | Ninfali, Chiara | Domínguez, Verónica | Andres-Manzano, Maria J. CNIC | Farràs, Marta | Esteve-Codina, Anna | Enrich, Carlos | Díaz-Crespo, Francisco J | Pintado, Belén | Escolà-Gil, Joan C | García de Frutos, Pablo | Andres, Vicente CNIC | Melgar-Lesmes, Pedro | Postigo, Antonio
Fecha de publicación
2023-12-14
Cita
Nat Commun. 2023 Dec 14;14(1):8316.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Accumulation of lipid-laden macrophages within the arterial neointima is a critical step in atherosclerotic plaque formation. Here, we show that reduced levels of the cellular plasticity factor ZEB1 in macrophages increase atherosclerotic plaque formation and the chance of cardiovascular events. Compared to control counterparts (Zeb1WT/ApoeKO), male mice with Zeb1 ablation in their myeloid cells (Zeb1∆M/ApoeKO) have larger atherosclerotic plaques and higher lipid accumulation in their macrophages due to delayed lipid traffic and deficient cholesterol efflux. Zeb1∆M/ApoeKO mice display more pronounced systemic metabolic alterations than Zeb1WT/ApoeKO mice, with higher serum levels of low-density lipoproteins and inflammatory cytokines and larger ectopic fat deposits. Higher lipid accumulation in Zeb1∆M macrophages is reverted by the exogenous expression of Zeb1 through macrophage-targeted nanoparticles. In vivo administration of these nanoparticles reduces atherosclerotic plaque formation in Zeb1∆M/ApoeKO mice. Finally, low ZEB1 expression in human endarterectomies is associated with plaque rupture and cardiovascular events. These results set ZEB1 in macrophages as a potential target in the treatment of atherosclerosis.
MESH
Plaque, Atherosclerotic | Atherosclerosis | Male | Mice | Humans | Animals | Down-Regulation | Mice, Knockout | Lipoproteins, LDL | Apolipoproteins E | Mice, Inbred C57BL | Zinc Finger E-box-Binding Homeobox 1
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
![Acceso Abierto Acceso Abierto](/themes/Mirage2/images/openAccess.png)
- Nombre:
- Atherosclerotic plaque develop ...
- Tamaño:
- 3.826Mb
- Formato:
- Descripción:
- Artículo