An Ex Vivo Model of Aortic Mechanical Failure

An Ex Vivo Model of Aortic Mechanical Failure

• Autor
• Sara Ventura
• Co-autores
• Leonardo Yuji Tanaka , Livia Teixeira , Renato S. Gaspar , Francisco Rafael Martins Laurindo , Julia M.F. Souza
• Resumo

• Introduction: Aneurysm and aortic dissection are vascular conditions that involve excessive remodelling of the artery. Our research group has discovered that the protein disulfide isomerase (PDIA1) may provide protection against aortic dissection and rupture in an in vivo model using (?-aminopropionitrile) BAPN, inhibition of lysyl oxidase (LOX) activity, and angiotensin 2. This finding suggests a novel mechanism that integrates redox homeostasis and biomechanics in vascular remodelling. However, existing models of aortic dissection involve time-consuming experiments in a large number of animals and do not intrinsically favor mechanistic investigation.  We sought to develop an ex vivo model that would allow better approaches to study mechanism of aortic dissection/rupture. Objective: The aim of this study is to establish and validate a mouse model of aortic ring rupture, in order to isolate and investigate the underlying molecular mechanisms involved, with a particular focus on redox signalling. Method: The study will be conducted on male C57/BL6 mice, 3 months old and weighing 250g. The mice will be randomly assigned to two groups: the control group and the group exposed to BAPN (500uM, incubated for 48 hours). The aortic rings will then be taken to the myograph for evaluation of viscoelasticity which will be assessed through stretch-tension correlation and length/tension values at mechanical failure and rupture. One-way analysis of variance (ANOVA) will be used to compare the differences between the groups. Ethical approval for the study will be obtained from the Animal Use Ethics Committee. Expected Results: BAPN treatment can cause disruption of the tunica media in large arteries, resulting in irregularities of elastin and collagen fibers as well as necrosis. These observed conditions resemble the lesions found in the large arteries of individuals with aortic dissection (AD). Utilizing an ex vivo analysis provides a means of assessing the molecular mechanisms involved with fewer variables, reducing the time, to final results, number of animals and allowing for the isolation of specific molecular pathways.

• Palavras-chave
• Aortic Dissection, Vascular remodeling, ?-aminopropionitrile (BAPN).
• Modalidade
• Pôster
• Área Temática
• Projetos Científicos