Models of Abdominal Aortic Aneurysm: Characterization and Clinical Applications

Chaer, Rabih A.; DeRubertis, Brian G.; Hynecek, Robert L.; Kent, K. Craig; Faries, Peter L.

doi:10.2310/6670.2006.00059

Cited by 9 publications

(2 citation statements)

References 73 publications

(86 reference statements)

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“…48 Further investigations in other animal models of AAA (elastase and CaCl 2 infusion) are needed to determine the clinical utility of Notch1 inhibition as a pharmacologic therapy. 11, 14, 52 …”

Section: Discussionmentioning

confidence: 99%

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

Hans

Koenig²,

Huang³

et al. 2012

ATVB

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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 (AngII)-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 AngII. Reconstitution of bone marrow-derived cells from Notch1+/−; Apoe−/− mice (donor) in lethally irradiated Apoe−/− mice (recipient) decreased 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. Additionally, there was an overall reduction in the inflammatory burden in the aorta of the Notch1+/−;Apoe−/− mice as compared to the Apoe−/− mice. Lastly, pharmacologic 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.

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Section: Discussionmentioning

confidence: 99%

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

Hans

Koenig²,

Huang³

et al. 2012

ATVB

View full text Add to dashboard Cite

show abstract

“…In contrast, mouse models of AAA utilize an acute injury to generate chronic aortic inflammation, leading to aneurysm formation in the following weeks 3 . The elastase and CaCl 2 models induce pathologies that resemble human AAA and are the preferred models to address the role of inflammatory cells and study specific gene deletions.…”

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confidence: 99%