Inhibition of Notch1 Signaling Reduces Abdominal Aortic Aneurysm in Mice by Attenuating Macrophage-Mediated Inflammation

• DOI: 10.1161/atvbaha.112.254219
• Publication Date: 2012-10-20T01:21:26Z
• Authors: Chetan P. Hans; Sara N. Koenig; Nianyuan Huang; Jeeyun Cheng; Susana Beceiro; Anuradha Guggilam; Helena Kuivaniemi; Santiago Partida-...; Vidu Garg
• Keywords: Male; Mice, Knockout; Arteritis; 0303 health sciences; Angiotensin II; Macrophages; Dipeptides; Haploinsufficiency; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Apolipoproteins E; Animals; Humans; Receptor, Notch1; 32 Ciencias médicas; Aortic Aneurysm, Abdominal; Signal Transduction

Activation of inflammatory pathways plays a critical role in the development abdominal aortic aneurysms (AAA). Notch1 signaling is significant regulator response; however, its AAA unknown.In an angiotensin II-induced mouse model AAA, activation was observed aneurysmal tissue Apoe(-/-) mice, and similar humans undergoing repair. haploinsufficiency significantly reduced incidence mice response to II. Reconstitution bone marrow-derived cells from Notch1(+/-);Apoe(-/-) (donor) lethally irradiated (recipient) decreased occurrence aneurysm. Flow cytometry immunohistochemistry demonstrated that prevented influx macrophages at site by causing defects macrophage migration proliferation. In addition, there overall reduction burden aorta compared with mice. Last, pharmacological inhibition also formation progression mice.Our data suggest levels protect against preventing recruitment attenuating aorta.