O64 ENHANCED EXPRESSION AND MEDIAL LAYER LOCALIZATION OF ELASTASE-2, AN ANGIOTENSIN ENZYME: IMPACT ON ABDOMINAL AORTIC ANEURYSM HALLMARKS IN MICE

Abdominal aortic aneurysm (AAA) is a pathological dilation of the abdominal aorta that can lead to death, with no pharmacological treatment available other than repair surgery. Continuous angiotensinII (AngII) infusion induces AAA in mice. Elastase-2 (ELA-2), a chymotrypsin-serine protease and an elastase family member, acts as an AngII enzyme in arteries and contributes to resistance arteries and vascular remodeling in animal models. Therefore, ELA-2 is a potential factor in AAA formation and/or development. We sought to investigate the expression and localization of ELA-2 in AAA-induced mice. Methods: Male wild-type (C57bl/6,WT) and ELA-2knockout (CELA-2aTm1Bdr; ELA-2KO) mice treated with saline (WT+Sal n=10, ELA-2KO+Sal, n=9) or AngII (1.500ng/kg/min, WT+AngII n=8, ELA-2KO+AngII n=8) for twenty-eight days by subcutaneously mini-pumps infusion. Vascular ultrasonography (US, Vevo2100) analyzed, before and after treatment, aortic expansion index, aortic systolic and diastolic diameter parameters. The immunofluorescence for ELA-2, aorta layer, and histologic staining to collagen, elastin, and fibrosis was analyzed. A correlation between ELA-2 and US was done. Results: WT+AngII mice developed AAA, and ELA-2KO mice did not have AAA by infusion of Ang II. Aorta ELA-2 expression up-regulated in WT-AngII vs. WT+Sal (p=0.0001). Aortic systolic diameter increased in the WT+AngII vs WT+Sal (0.8vs.1.5 mm, p<0.0001). Aortic diastolic diameter increases in the WT+AngII vs WT+Sal (1.2 vs.0.6 mm, p<0.0001). The aortic expansion index decreases in WT+Ang II vs WT+Sal (11.4 vs.17.1%, p=0.0008). WT+AngII aorta has higher collagen deposition and fibrosis and lower elastin than WT+Saline (p=0.001). ELA-2KO+AngII vs. ELA-2KO+SAL showed no difference in elastin, collagen, and fibrosis. The analyzed parameters characteristic of AAA showed a positive correlation with ELA-2 in aorta middle layer in WT+AngII, where AAA develops. Conclusion: ELA-2 expression is up-regulated in AAA mice’s aorta and may contribute to developing aneurysms. ELA-2KO might be less susceptible to developing AAA induced by AngII infusion. Therefore, ELA-2 plays a significant role in AAA pathophysiology and could be a potential target for therapeutic treatment to prevent AAA development.