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Updated: Jan 12, 2026
Mouse Abdominal Aortic Aneurysm Model Induced by Perivascular Application of Elastase
Published on: February 11, 2022
Elastase-2 deletion prevents vascular remodeling and abdominal aortic aneurysm development in a mice model induced by
Fabiola Mestriner1, Vinicius Flora Dugaich1, Pedro Brüch Dantas1
1Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Abstract:
Abdominal aortic aneurysm (AAA) involves the remodeling of the aortic wall extracellular matrix (ECM), compromising biomechanical support and increasing the risk of aortic dissection and rupture. Activation of the renin-angiotensin system (RAS), particularly the synthesis of angiotensin II (Ang II), plays a fundamental role in AAA initiation and progression. Elastase-2 (ELA-2), a chymotrypsin-like serine protease, contributes to tissue Ang II generation and may be a key player in AAA pathophysiology. This study investigated the effects of ELA-2 deletion in a murine model of angiotensin II-induced AAA, with particular focus on determining whether ELA-2 modulates vascular contractility and aortic relaxation in wild-type mice and whether these effects are absent in ELA-2 knockout mice. We additionally examined the cellular alterations within the aortic wall that contribute to increased reactive oxygen species generation during AAA development. Male C57BL/6 J (wild-type, WT) and ELA-2 knockout (ELA-2KO) mice, aged 10 to 15 weeks, were infused with Ang II (1500 ng/kg/min) for 28 days to induce AAA formation. Wild-type (WT) mice developed AAA, as evidenced by aortic dilation, structural remodeling, fibrosis, and inflammation. In contrast, ELA-2KO mice showed markedly reduced pathological changes following Ang II-induced AAA. Histological and biochemical analyses of the abdominal aorta revealed enhanced gelatinolytic activity, macrophage infiltration, and oxidative stress in WT mice, all of which were significantly attenuated in ELA-2KO mice. Furthermore, transcriptional profiling demonstrated that ELA-2 deletion maintained a contractile VSMC phenotype, suggesting a protective effect against maladaptive vascular remodeling. In summary, ELA-2 deficiency prevented Ang II- induced AAA formation and pathological vascular remodeling, highlighting its potential as a therapeutic target to mitigate AAA progression.
