Abstract
Objective
Abdominal aortic aneurysm (AAA) is a significant medical problem with a high mortality rate. Nevertheless, the underlying mechanism for the progression and regression of AAA is unknown.
Methods
Experimental model of AAA was first created by porcine pancreatic elastase incubation around the infrarenal aorta of C57BL/6 mice. Then, AAA progression and regression were evaluated based on the diameter and volume of AAA. The aortas were harvested for hematoxylin-eosin staining (HE), orcein staining, sirius red staining, immunofluorescence analysis and perls’ prussian blue staining at the indicated time point. Finally, β-aminopropionitrile monofumarate (BAPN) was used to explore the underlying mechanism of the regression of AAA.
Results
When we extended the observation period to 100 days, we not only observed an increase in the AAA diameter and volume in the early stage, but also a decrease in the late stage. Consistent with AAA diameter and volume, the aortic thickness showed the same tendency based on HE staining. The elastin and collagen content first degraded and then regenerated, which corresponds to the early deterioration and late regression of AAA. Then, endogenous up-regulation of lysyl oxidase (LOX) was detected, accompanying the regression of AAA, as detected by an immunofluorescent assay. BAPN and LOX inhibitor considerably inhibited the regression of AAA, paralleling the degradation of elastin lamella and collagen.
Conclusion
Taken together, we tentatively conclude that endogenous re-generation of LOX played an influential role in the regression of AAA. Therefore, regulatory factors on the generation of LOX exhibit promising therapeutic potential against AAA.
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This work was supported by grants from the National Natural Science Foundation of China (No. 81770478 and No. 81970395), the Shanghai Science and Technology Development Foundation (No. 21S21901900), Inter-governmental Science and Technology Innovation Cooperation Program, Ministry of Science and Technology of China (No. 2021YFE0111300) and the Biological Resources Programme, Chinese Academy of Sciences (No. KFJ-BRP-008).
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Ding, Yc., Zhang, Xj., Zhang, Jx. et al. Progression and Regression of Abdominal Aortic Aneurysms in Mice. CURR MED SCI 41, 901–908 (2021). https://doi.org/10.1007/s11596-021-2425-z
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DOI: https://doi.org/10.1007/s11596-021-2425-z