ABSTRACT
Apolipoprotein knockout (ApoE-/-) and CD57BL/6J mouse models of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) are commonly used in AAA research. However, the similarities and differences in the molecular mechanisms of AAA in these two genotypes have not been reported. In our study, we analyzed proteomics data from ApoE-/- and CD57BL/6J mouse models of Ang II-induced AAA and control mice by LC-MS/MS. Gene set enrichment analysis (GSEA) of differentially abundance proteins (DAPs) in the ApoE-/- or CD57BL/6J mouse groups was performed in R software, and infiltration of immune cells in groups was assessed. DAP that showed the same trend in abundance in ApoE-/- and CD57BL/6J mice (S-DAP) were identified and subjected to GO enrichment, KEGG pathway, and connectivity map (CMap) analyses. The protein-protein interaction (PPI) network of the S-DAP was drawn, the key S-DAP were identified by MCODE, and the transcription factors (TFs) of crucial S-DAP were predicted by iRegulon in Cytoscape. Male ApoE-/- and CD57BL/6J mouse models of Ang II-induced AAA are commonly used in AAA research, and extracellular matrix organization is associated with AAA in both of these models. However, there are some differences between the mechanisms underlying AAA in these two genotypes, and these differences need to be considered when studying AAA and selecting models. SIGNIFICANCE: Our research provided the first insight into the similarity and differential mechanisms of Ang II infused AAA models using ApoE-/- and CD57BL/6J mice. This study might provide the some advises for the selection of Ang II infused AAA models for further AAA researches.
Subject(s)
Angiotensin II , Aortic Aneurysm, Abdominal , Angiotensin II/adverse effects , Animals , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/metabolism , Apolipoproteins E/adverse effects , Apolipoproteins E/genetics , Chromatography, Liquid , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Proteomics , Tandem Mass Spectrometry , Transcription FactorsABSTRACT
O objetivo do trabalho foi criar um modelo experimental animal de indução de aneurisma em aorta abdominal, identificando qual a droga e técnica de escolha, para a pesquisa de patogenia e tempo de desenvolvimento do aneurisma. Foram utilizados 48 ratos Wistar machos adultos, que foram submetidos a laparotomia mediana com aplicação das drogas de forma intraluminal ou periarterial. As drogas utilizadas foram cloreto de cálcio a 0,9 ou 5,0 molar (M) e cloreto de sódio 0,9 por cento ou 7,5 por cento. O trabalho foi realizado em duas etapas, nas quais se preocupou identificar a melhor droga na primeira etapa e a melhor técnica na segunda. Vinte e sete ratos foram divididos em grupos de três animais cada, variando a droga e a metodologia de aplicação na primeira etapa. Na segunda etapa utilizaram-se dois grupos com dez animais em cada, usando-se a solução de cloreto de cálcio a 5,0M com aplicação periarterial ou intraluminal...