Cross-species scRNA-seq finds ideal mouse models for aortic dissection mechanisms.

Aortic dissection is a life-threatening cardiovascular disease whose complex cellular pathophysiology is studied using various mouse models. To systematically evaluate their fidelity, we performed cross-species single-cell RNA sequencing, integrating data from human aortic dissection with five mouse models (BAPN, Ang-II, Ang-II apoE(-/-), elastase, and CaCl(2)). Comparative analysis across four key cell types revealed model-specific transcriptional parallels to human disease. The BAPN model recapitulated human pro-inflammatory and lipid-associated macrophage states, as well as pro-inflammatory fibroblast signatures. The Ang-II apoE(-/-) model mimicked pathogenic vascular smooth muscle cell phenotypes, particularly lipid-associated and oxidative stress states. Endothelial cell dysfunction was a conserved feature across all models. Our study provides a single-cell-based comparative framework highlighting model-specific transcriptional similarities to human aortic dissection.