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. 2021 Nov 15;11:22278. doi: 10.1038/s41598-021-01735-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Increase of the activity of cathepsin S in the aortic wall of Apelin-knockout mice (KO-APL mice, grey bars, n = 8) as compared wild-type mice (WT, white bar, n = 8). (A) Hematoxylin–eosin (H&E) staining and autofluorescence of elastin showing fragmentation of inner laminae (L1–L4), a characteristic of aneurism development. (B) mRNA expression of matrix metalloproteinases (MMPs) -9 and 12. Neutrophil elastase (NE), Cathepsin S (Cath. S). (C) Bar plots indicate neutrophil elastase activity (left) and cathepsin S activity (right). (D) Graph depicting linear relationships between neutrophil elastase activity and plasma EDP levels (right) and mean laminar rupture number obtained for each animal studied (right, WT, white dots; KO, grey dots). (E) Graph depicting linear relationships between cathepsin S activity (left) and plasma EDP levels and the mean laminar rupture number obtained for each animal studied (right, WT, white circles; KO, grey circles). (F) Immunostaining against cathepsin S showing accumulation in lumen of aorta (L) near the tunica intima and between the tunica media and tunica adventitia (arrows). (G) Graph depicting linear relationships between cathepsin S staining and laminar rupture number (left) and elastin autofluorescence (right, WT, white circles; KO, grey circles). The results are the mean ± SEM. Statistically significant differences (Mann–Whitney).