Establishment of a murine chronic proximal thoracic aortic aneurysm model by combining periaortic elastase...

This study aimed to develop a chronic proximal thoracic aortic aneurysm (PTAA) model by combining periaortic elastase application with oral administration of 3-aminopropionitrile fumarate salt (BAPN) after surgery. Sixty 8-week-old C57BL/6J male mice were divided into four groups: Sham, Sham + BAPN, Elastase, and Elastase + BAPN. High-resolution micro-ultrasound was performed on days 7, 14, 21, 28, 56, and 90 post-operation to measure aortic diameter. Histopathological, transcriptomic, and bioinformatics analyses were conducted to assess the model's relevance to human PTAA. The operative mortality rate was 10 % (6/60). During follow-up, 4 animals in the elastase + BAPN group and 1 in the elastase group died from aortic rupture. Significant continuous dilation of the proximal thoracic aorta was observed only in the elastase + BAPN group, with average dilation rates of 116.60 %, 178.99 %, and 231.90 % on days 28, 56, and 90, respectively, compared to 66.46 %, 61.13 %, and 68.73 % in the elastase group. Histopathology revealed greater aortic wall thickening, collagen deposition, MMP2 expression, elastin degradation, smooth muscle cell loss, calcification, and immune cell infiltration in the elastase + BAPN group. Transcriptomic analysis identified 3039 differentially expressed genes, enriched in immune and inflammation-related pathways. Weighted gene co-expression network analysis showed significant overlap in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment results between human and murine PTAA-related gene modules which were most positively correlated with PTAA diameters. This study establishes a chronic PTAA model that mimics key features of human disease, providing a valuable tool for investigating PTAA mechanisms and developing new therapies.