Display options
Cite
Ding YC, Zhang XJ, Zhang JX, et al. Progression and Regression of Abdominal Aortic Aneurysms in Mice. Curr Med Sci. 2021;41(5):901-908doi: 10.1007/s11596-021-2425-z.
Ding, Y. C., Zhang, X. J., Zhang, J. X., Zhai, Z. Y., Zhang, M. X., & Jiang, B. H. (2021). Progression and Regression of Abdominal Aortic Aneurysms in Mice. Current medical science, 41(5), 901-908. https://doi.org/10.1007/s11596-021-2425-z
Ding, Yu-Chao, et al. "Progression and Regression of Abdominal Aortic Aneurysms in Mice." Current medical science vol. 41,5 (2021): 901-908. doi: https://doi.org/10.1007/s11596-021-2425-z
Ding YC, Zhang XJ, Zhang JX, Zhai ZY, Zhang MX, Jiang BH. Progression and Regression of Abdominal Aortic Aneurysms in Mice. Curr Med Sci. 2021 Oct;41(5):901-908. doi: 10.1007/s11596-021-2425-z. Epub 2021 Oct 13. PMID: 34643880.
Copy Download .nbib Format: NLM
Share it on

Curr Med Sci. 2021 Oct;41(5):901-908. doi: 10.1007/s11596-021-2425-z. Epub 2021 Oct 13.

Progression and Regression of Abdominal Aortic Aneurysms in Mice.

Current medical science

Yu-Chao Ding, Xian-Jing Zhang, Ji-Xiu Zhang, Zi-Yi Zhai, Mei-Xia Zhang, Bao-Hong Jiang

Affiliations

  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  2. The College of Basic Medical Science, China Medical University, Shenyang, 110122, China.
  3. The College of Basic Medical Science, China Medical University, Shenyang, 110122, China. [email protected].
  4. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].

PMID: 34643880 DOI: 10.1007/s11596-021-2425-z

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.

© 2021. Huazhong University of Science and Technology.

Keywords: abdominal aortic aneurysm; disease progression; disease regression; elastogenesis; lysyl oxidase

References

  1. Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): A report of the American college of cardiology foundation/American heart association task force on practice guidelines. Circulation, 2011,124(18): 2020–2045 - PubMed
  2. Thompson MM. Controlling the expansion of abdominal aortic aneurysms. Br J Surg, 2003,90(8):897–898 - PubMed
  3. Wu J, Wang J, Li XO, et al. MicroRNA-145 Mediates the Formation of Angiotensin II-Induced Murine Abdominal Aortic Aneurysm. Heart Lung Circ, 2017, 26(6):619–626 - PubMed
  4. Golledge J, Norman PE. Current status of medical management for abdominal aortic aneurysm. Atherosclerosis, 2011,217(1):57–63 - PubMed
  5. Sakalihasan N, Limet R, Defawe OD. Abdominal aortic aneurysm. Lancet, 2005,365(9470):1577–1589 - PubMed
  6. Wallinder J, Georgiou A, Wanhainen A, et al. Prevalence of Synchronous and Metachronous Aneurysms in Women With Abdominal Aortic Aneurysm. Eur J Vasc Endovasc Surg, 2018,56(3):435–440 - PubMed
  7. He BM, Chai XP, He ZB, et al. HDL quantity and function are potential therapeutic targets for abdominal aortic aneurysm. Int J Cardiol, 2014,176(3):1070–1071 - PubMed
  8. Golledge J, Muller J, Daugherty A, et al. Abdominal aortic aneurysm: pathogenesis and implications for management. Arterioscler Thromb Vasc Biol, 2006, 26(12):2605–2613 - PubMed
  9. Golledge J, Norman PE, Murphy MP, et al. Challenges and opportunities in limiting abdominal aortic aneurysm growth. J Vasc Surg, 2017,65(1):225–233 - PubMed
  10. Rabkin SW. The role matrix metalloproteinases in the production of aortic aneurysm. Prog Mol Biol Transl Sci, 2017,147:239–265 - PubMed
  11. Xiong J, Wang SM, Chen LH, et al. Elastic fibers reconstructed using adenovirus-mediated expression of tropoelastin and tested in the elastase model of abdominal aortic aneurysm in rats. J Vasc Surg, 2008, 48(4):965–973 - PubMed
  12. Kielty CM, Sherratt MJ, Shuttleworth CA. Elastic fibres. J Cell Sci, 2002,115(Pt 14):2817–2828 - PubMed
  13. Daugherty A, Cassis LA. Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol, 2004, 24(3):429–434 - PubMed
  14. Zaragoza C, Gomez-Guerrero C, Martin-Ventura JL, et al. Animal models of cardiovascular diseases. J Biomed Biotechnol, 2011,2011:497841 - PubMed
  15. Bhamidipati CM, Mehta GS, Lu G, et al. Development of a novel murine model of aortic aneurysms using peri-adventitial elastase. Surgery, 2012,152(2):238–246 - PubMed
  16. Flurkey K, Currer JM, Harrison DE. In: The Mouse in Biomedical Research 2nd Edition. Fox JG, et al, eds. The Mouse in Aging Research. Burlington: American College Laboratory Animal Medicine (Elsevier), 2007: 637–672 - PubMed
  17. Naito S, VonEschenbach AC, Giavazzi R, et al. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res, 1986,46(8):4109–4115 - PubMed
  18. Hu CJ, Zhou L, Cai Y. Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2. Cancer Biol Ther, 2014,15(3):279–288 - PubMed
  19. Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev, 2009,89(3):957–989 - PubMed
  20. Kavazos K, Nataatmadja M, Wales KM, et al. Dietary Supplementation with Omega-3 Polyunsaturated Fatty Acids Modulate Matrix Metalloproteinase Immunoreactivity in a Mouse Model of Pre-abdominal Aortic Aneurysm. Heart Lung Circ, 2015,24(4):377–385 - PubMed
  21. Arnaud C, Bouyon S, Recoquillon S, et al. Nonmuscle myosin light chain kinase: A key player in intermittent hypoxia-induced vascular alterations. J Am Heart Assoc, 2018,7(3):e007893 - PubMed
  22. Coquand-Gandit M, Jacob MP, Fhayli W, et al. Chronic treatment with minoxidil induces elastic fiber neosynthesis and functional improvement in the aorta of aged mice. Rejuvenation Res, 2017,20(3):218–230 - PubMed
  23. Kagan HM, Li W. Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem, 2003,88(4):660–672 - PubMed
  24. Maki JM, Rasanen J, Tikkanen H, et al. Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. Circulation, 2002,106(19):2503–2509 - PubMed
  25. Yokoyama U, Ishikawa Y. In: Akashi M, eds. Engineered Cell Manipulation for Biomedical Application. Tokyo: Springer, 2014:159–174. - PubMed
  26. Schmelzer CEH, Heinz A, Troilo H, et al. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. Faseb J, 2019,33(4):5468–5481 - PubMed
  27. Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med, 2010,16(9):1009–1017 - PubMed
  28. Bignon M, Pichol-Thievend C, Hardouin J, et al. Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane. Blood, 2011,118(14):3979–3989 - PubMed
  29. Lee VS, Halabi CM, Hoffman EP, et al. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci USA, 2016,113(31):8759–8764 - PubMed
  30. Yoshimura K, Aoki H, Ikeda Y, et al. Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase in mice. Ann N Y Acad Sci, 2006, 1085:74–81 - PubMed

Publication Types