Increased atherosclerotic plaque in AOC3 knock-out in ApoE−/− mice and characterization of AOC3 in atherosclerotic human coronary arteries - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Frontiers in Cardiovascular Medicine Année : 2022

Increased atherosclerotic plaque in AOC3 knock-out in ApoE−/− mice and characterization of AOC3 in atherosclerotic human coronary arteries

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Introduction Amine oxidase copper containing 3 (AOC3) displays adhesion between leukocytes and endothelial cells and enzymatic functions. Given its controversial role in atherogenesis, we proposed to investigate the involvement of AOC3 in the formation of atherosclerotic plaques in ApoE −/− AOC3 −/− mice and human coronary arteries. Methods Lesions, contractile markers, and AOC3 were studied in aortic tissues from 15- and 25-week-old mice and different stages of human coronary atherosclerotic arteries by immunohistochemistry (IHC) and/or western blot. Human VSMCs, treated or not with LJP1586, an AOC3 inhibitor, were used to measure differentiation markers by qPCR. AOC3 co-localization with specific cell markers was studied by using confocal microscopy in mice and human samples. Results At 15 weeks old, the absence of AOC3 was associated with increased lesion size, α-SMA, and CD3 staining in the plaque independently of a cholesterol modification. At 25 weeks old, advanced plaques were larger with equivalent staining for α-SMA while CD3 increased in the media from ApoE −/− AOC3 −/− mice. At both ages, the macrophage content of the lesion was not modified. Contractile markers decreased whereas MCP-1 appeared augmented only in the 15-week-old ApoE −/− AOC3. AOC3 is mainly expressed by mice and human VSMC is slightly expressed by endothelium but not by macrophages. Conclusion AOC3 knock-out increased atherosclerotic plaques at an early stage related to a VSMC dedifferentiation associated with a higher T cells recruitment in plaques explained by the MCP-1 augmentation. This suggests that AOC3 may have an important role in atherosclerosis independent of its canonical inflammatory effect. The dual role of AOC3 impacts therapeutic strategies using pharmacological regulators of SSAO activity.
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hal-03836482 , version 1 (04-11-2022)

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Anna Filip, Soraya Taleb, Rümeyza Bascetin, Mohammad Jahangiri, Matthieu Bardin, et al.. Increased atherosclerotic plaque in AOC3 knock-out in ApoE−/− mice and characterization of AOC3 in atherosclerotic human coronary arteries. Frontiers in Cardiovascular Medicine, 2022, 9, pp.848680. ⟨10.3389/fcvm.2022.848680⟩. ⟨hal-03836482⟩
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