DOI: 10.1161/circ.148.suppl_1.13322 ISSN: 0009-7322

Abstract 13322: Administrating the Anti-Apoptosis Inhibitor of Macrophage Antibody Prevents Aortic Aneurysm Progression in Mice

Taro Fujii, Aika Yamawaki-Ogata, Sachie Terazawa, Yuji Narita, Masato Mutsuga
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Our previous report has shown that macrophages play vital roles in developing aortic aneurysms (AA). Apoptosis inhibitor of macrophage (AIM) secreted from macrophages is known to induce apoptosis resistance of macrophages and exacerbate chronic inflammation, which leads to arteriosclerosis. However, it is unclear the role of AIM in AA.

Hypothesis: We hypothesized that administering the anti-AIM antibody could prevent eventual AA progression via inhibiting chronic inflammation and promoting apoptosis of macrophages.

Methods: The AA was induced in apolipoprotein E deficient mice by subcutaneous angiotensin II (ATII) infusion. Along with ATII infusion, an anti-murine AIM monoclonal antibody or anti-murine IgG antibody was injected intraperitoneally. Mice were divided randomly into two groups: (i) AIM group; weekly anti-AIM antibody injection (n=10), and (ii) IgG group; anti-IgG antibody injection as control (n=14). All animals were euthanized 4 weeks after study initiation.

Results: There were two deaths in the control group and one in the AIM group. None of the deaths were aorta-related. Compared with the IgG group, the AIM group exhibited reduced AA enlargement (aortic diameter at four weeks: AIM 2.1 vs. IgG 2.7 mm, p = 0.012), less loss of construction of the elastic lamellae, reduction protein expression levels of various inflammatory response including IL-6, TNF-α and MCP-1, a decrease in the number of AIM-positive cells and inflammatory M1 macrophages (AIM: 1.4 vs. 8.0 %, p = 0.004, M1 macrophages: 24.5 vs. 55.7 %, p = 0.017), and higher expression of caspase-3 (22.8 vs. 10.5 %, p = 0.019) in the aortic wall.

Conclusions: Our results suggested that anti-AIM antibody therapy mitigated AA progression by controlling inflammation and promoting apoptosis.

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