Mouse models of aortic aneurysm and dissection: pathophysiological insights and translational perspectives.

BACKGROUND

Aortic aneurysm (AA) and aortic dissection (AD) are catastrophic aortic disorders characterized by progressive structural weakening or acute medial tearing, often resulting in rupture and high mortality. Their complex and heterogeneous pathogenesis-spanning extracellular matrix degradation, vascular smooth muscle cell dysfunction, inflammation, and dysregulated signaling-necessitates robust experimental systems. Diverse animal and engineered models have been developed to capture key features of these diseases, yet each recapitulates only specific aspects of human pathology.

AIM OF REVIEW: This review aims to: (1) systematically summarize current experimental models of AA and AD, including chemical, genetic, and combined systems; (2) provide a decision tree for selecting mouse models of AA and AD for vascular research; (3) evaluate model-specific strengths, limitations, and translational relevance, while highlighting emerging technologies such as vascular organoids and engineered 3D platforms that may bridge gaps between preclinical research and human disease.

KEY SCIENTIFIC CONCEPTS OF REVIEW: This review presents an integrated framework linking aortic pathology to model-specific mechanisms, illustrating how extracellular matrix (ECM) failure, smooth muscle cell remodeling, inflammation, and biomechanical stress drive AA and AD. We further emphasize the translational hierarchy across mouse, large-animal, and organoid models, providing guidance for rational model selection in therapeutic discovery. By systematically summarizing classical and emerging mouse models of AA and AD, this review provides a structured framework to guide model selection and future mechanistic studies in the field.