2026-07-22T01:50:09Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/168402024-09-27T08:48:18Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Martinez-Campanario, M C author Cortés, Marlies author Moreno-Lanceta, Alazne author Han, Lu author Ninfali, Chiara author Domínguez, Verónica author Andres-Manzano, Maria J. author Farràs, Marta author Esteve-Codina, Anna author Enrich, Carlos author Díaz-Crespo, Francisco J author Pintado, Belén author Escolà-Gil, Joan C author García de Frutos, Pablo author Andres, Vicente author Melgar-Lesmes, Pedro author Postigo, Antonio author 2023-12-14 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. Nat Commun. 2023 Dec 14;14(1):8316. 10.1038/s41467-023-43896-7 2041-1723 Nature communications 38097578 http://hdl.handle.net/20.500.12105/16840 Atherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation.