Inducing aortic aneurysm/dissection in zebrafish: evaluating the efficacy of β-Aminopropionic Nitrile as a model.
Jiarui ZhangYaowen LiangWeiyue ZengXiao-Yan GaoDingchen WangCong MaiZhuoheng LinHaishan ZhaoXin LiPublished in: Animal cells and systems (2024)
Aortic aneurysm/dissection (AAD) poses a life-threatening cardiovascular emergency with complex mechanisms and a notably high mortality rate. Zebrafish (Danio rerio) serve as valuable models for AAD due to the conservation of their three-layered arterial structure and genome with that of humans. However, the existing studies have predominantly focused on larval zebrafish, leaving a gap in our understanding of adult zebrafish. In this study, we utilized β-Aminopropionic Nitrile (BAPN) impregnation to induce AAD in both larval and adult zebrafish. Following induction, larval zebrafish exhibited a 28% widening of the dorsal aortic diameter ( p < 0.0004, n = 10) and aortic arch malformations, with a high malformation rate of 75% (6/8). Conversely, adult zebrafish showed a 41.67% (5/12) mortality rate 22 days post-induction. At this time point, the dorsal aortic area had expanded by 2.46 times ( p < 0.009), and the vessel wall demonstrated significant thickening (8.22 ± 2.23 μM vs. 26.38 ± 10.74 μM, p < 0.05). Pathological analysis revealed disruptions in the smooth muscle layer, contributing to a 58.33% aneurysm rate. Moreover, the expression levels of acta2, tagln, cnn1a, and cnn1b were decreased, indicating a weakened contractile phenotype. Transcriptome sequencing showed a significant overlap between the molecular features of zebrafish tissues post-BAPN treatment and those of AAD patients. Our findings present a straightforward and practical method for generating AAD models in both larval and adult zebrafish using BAPN.
Keyphrases
- smooth muscle
- aortic aneurysm
- spinal cord
- gene expression
- healthcare
- emergency department
- aedes aegypti
- heart failure
- cardiovascular disease
- left ventricular
- type diabetes
- coronary artery
- risk factors
- cardiovascular events
- coronary artery disease
- machine learning
- convolutional neural network
- skeletal muscle
- end stage renal disease
- prognostic factors
- ejection fraction
- chronic kidney disease
- pulmonary artery
- single molecule
- patient reported
- combination therapy
- ion batteries