Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/44414
Título: Inhibition of Notch1 signaling reduces abdominal aortic aneurysm in mice by attenuating macrophage-mediated inflammation
Autores/as: Hans, Chetan P.
Koenig, Sara N.
Huang, Nianyuan
Cheng, Jeeyun
Beceiro Casas, Susana 
Guggilam, Anuradha
Kuivaniemi, Helena
Partida-Sánchez, Santiago
Garg, Vidu
Clasificación UNESCO: 32 Ciencias médicas
Fecha de publicación: 2012
Editor/a: 1079-5642
Publicación seriada: Arteriosclerosis, Thrombosis, and Vascular Biology 
Resumen: Objective: Activation of inflammatory pathways plays a critical role in the development of abdominal aortic aneurysms (AAA). Notch1 signaling is a significant regulator of the inflammatory response; however, its role in AAA is unknown. Methods and Results: In an angiotensin II–induced mouse model of AAA, activation of Notch1 signaling was observed in the aortic aneurysmal tissue of Apoe−/− mice, and a similar activation of Notch1 was observed in aneurysms of humans undergoing AAA repair. Notch1 haploinsufficiency significantly reduced the incidence of AAA in Apoe−/− mice in response to angiotensin II. Reconstitution of bone marrow–derived cells from Notch1+/−;Apoe−/− mice (donor) in lethally irradiated Apoe−/− mice (recipient) decreased the occurrence of aneurysm. Flow cytometry and immunohistochemistry demonstrated that Notch1 haploinsufficiency prevented the influx of inflammatory macrophages at the aneurysmal site by causing defects in macrophage migration and proliferation. In addition, there was an overall reduction in the inflammatory burden in the aorta of the Notch1+/−;Apoe−/− mice compared with the Apoe−/− mice. Last, pharmacological inhibition of Notch1 signaling also prevented AAA formation and progression in Apoe−/− mice. Conclusion: Our data suggest that decreased levels of Notch1 protect against the formation of AAA by preventing macrophage recruitment and attenuating the inflammatory response in the aorta.
URI: http://hdl.handle.net/10553/44414
ISSN: 1079-5642
DOI: 10.1161/ATVBAHA.112.254219
Fuente: Arteriosclerosis, Thrombosis, and Vascular Biology [ISSN 1079-5642], v. 32, p. 3012-3023
Colección:Artículos
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