Which Mouse Model of Abdominal Aortic Aneurysm Deserves Triple A Status?

Tedjawirja, Victoria N.; Waard, Vivian de

doi:10.1016/j.ejvs.2019.07.008

Cited by 6 publications

(9 citation statements)

References 15 publications

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“…In the former, the abdominal aorta is locally infused with porcine pancreatic elastase (elastase or PPE). Severe degradation of the ECM occurs, triggering an inflammatory response and MMP upregulation [ 74 , 75 ]. A nondissecting AAA will typically form in two weeks, making this a suitable model for prevention studies.…”

Section: Animal Models Of Aaamentioning

confidence: 99%

“…Genetically modified ( ApoE −/− or LDLR −/−) mice are more susceptible to AAA formation with AngII infusion as compared to C57BL/6 mice [ 78 , 79 ]. The AngII infusion triggers a pro-inflammatory cascade that drives SMC apoptosis, ECM degradation, and aortic dilation [ 74 , 80 , 81 ]. An AAA will continue to expand until AngII infusion is discontinued, thereby making this model more appealing for intervention-based studies.…”

Section: Animal Models Of Aaamentioning

confidence: 99%

“…The AngII model appears to resemble human pathology more closely in some of the features it induces such as luminal expansion, thrombosis, ECM degradation, and prominent inflammatory markers [ 1 , 73 , 74 , 80 – 82 ]. However, it shows dissection of the medial aorta, whereas the human condition presents as nondissecting AAA.…”

Section: Animal Models Of Aaamentioning

confidence: 99%

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Development of pharmacotherapies for abdominal aortic aneurysms

Weaver¹,

Loftin²,

Zhan³

2022

Biomedicine & Pharmacotherapy

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Section: Animal Models Of Aaamentioning

confidence: 99%

Section: Animal Models Of Aaamentioning

confidence: 99%

Section: Animal Models Of Aaamentioning

confidence: 99%

See 1 more Smart Citation

Development of pharmacotherapies for abdominal aortic aneurysms

Weaver¹,

Loftin²,

Zhan³

2022

Biomedicine & Pharmacotherapy

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“…Conventional genomics and proteomics only analyze the pathogeneses of diseases at the organizational level [7, 8].The emergence of single-cell RNA sequencing (sc-RNA seq) technology has provided new opportunities for research. It reveals the heterogeneity of complex cell populations and intercellular interaction according to pivotal characteristic genes.There were three classic mouse AAA models commonly used in the laboratory, including porcine pancreatic elastase-induced AAA models, Ang II-induced AAA models, and calcium chloride (CaCl 2 )impregnated AAA models [9]. All three have their own advantages and disadvantages, and a comprehensive study of AAA using different models is necessary.…”

mentioning

confidence: 99%

“…There were three classic mouse AAA models commonly used in the laboratory, including porcine pancreatic elastase-induced AAA models, Ang II-induced AAA models, and calcium chloride (CaCl 2 )impregnated AAA models [9]. All three have their own advantages and disadvantages, and a comprehensive study of AAA using different models is necessary.…”

mentioning

confidence: 99%

Single-cell RNA Sequencing Technology Revealed the Pivotal Role of Fibroblast Heterogeneity in Ang II-Induced Abdominal Aortic Aneurysms

Weng

Lou

Bao

et al. 2021

Preprint

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Aim: The mechanism of abdominal aortic aneurysm (AAA) has not been fully elucidated. In this study, we aimed to map the cellular heterogeneity, molecular alteration, and functional transformation of angiotensin (Ang) II-induced AAA in mice based on single-cell RNA sequencing (sc-RNA seq) technology.Method: Single-cell RNA sequencing was performed on suprarenal abdominal aorta from male APOE-/- C57BL/6 mice of Ang II-induced AAA and shame models. Immunohistochemistry was used to determine the pathophysiological characteristics of AAA, and sc-RNA seq was used to determine the heterogeneity and phenotypic transformation of all cell types. A single-cell trajectory was performed to predict the differentiation of fibroblasts. Finally ligand–receptor analysis was used to evaluate intercellular communication between fibroblasts and smooth muscle cells.Results: More than 27,000 cells were isolated and 25 clusters representing 8 types of cells were identified, including fibroblasts, macrophages, endothelial cells, smooth muscle cells, T lymphocytes, B lymphocytes, granulocytes, and natural killer cells. During AAA progression, the function and phenotype of different type cells altered separately. The pro-inflammatory function of inflammatory cells was enhanced. The proliferation phenotype degreased while pro-inflammatory, regeneration and damage-related phenotypes increased in endothelial cells. Smooth muscle cells also transformed from contractile to secretory phenotype. The alterations of fibroblasts were the most conspicuous according sub-group clustering analysis. Single-cell trajectory revealed the critical reprogramming genes of fibroblasts mainly enriched in regulation of immune system. Finally, the ligand–receptor analysis confirmed that increases in secondary collagen synthesis led by fibroblasts were one of the most prominent characteristics of Ang II-induced AAA.Conclusion: Our study revealed the cellular heterogeneity of Ang II-induced AAA. Fibroblasts may play a central role in Ang II-induced AAA progression according multiple biological functions including immune regulation and extracellular matrix metabolic balance. Our study may provide us with a different perspective on the etiology and pathogenesis of AAA.

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Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

et al. 2023

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Development of abdominal aortic aneurysms (AAA) enhances lesion group‐2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/flIl7rCre/+ mice or induced ILC2 depletion in Icosfl‐DTR‐fl/+Cd4Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild‐type (WT) mice, but not ILC2 from Il5−/− mice induces EOS differentiation in bone‐marrow cells from Rorafl/flIl7rCre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5−/− and Il13−/− mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5−/− mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5−/− ILC2 slows AAA growth in Rorafl/flIl7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

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Which Mouse Model of Abdominal Aortic Aneurysm Deserves Triple A Status?

Cited by 6 publications

References 15 publications

Development of pharmacotherapies for abdominal aortic aneurysms

Development of pharmacotherapies for abdominal aortic aneurysms

Single-cell RNA Sequencing Technology Revealed the Pivotal Role of Fibroblast Heterogeneity in Ang II-Induced Abdominal Aortic Aneurysms

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

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