Cellular Heterogeneity in Aortic Aneurysm and Dissection: Molecular Mechanisms and Therapeutic Opportunities - PubMed
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- #therapeutic opportunities
- #aortic aneurysm
- Aortic aneurysm and dissection (AAD) are life-threatening conditions lacking effective pharmacological strategies despite advances in surgical and endovascular management.
- The pathogenesis of AAD is driven by cellular heterogeneity in the aortic wall, involving diverse cell subpopulations like smooth muscle cells, endothelial cells, immune cells, and fibroblasts.
- Smooth muscle cell heterogeneity includes embryonic origins and phenotypic switching into states such as fibroblast-like, proliferative, macrophage-like, osteochondrogenic, stressed, and adipocyte-like, which drive ECM degradation, inflammation, and metabolic reprogramming.
- Dysfunctional endothelial cells compromise barrier integrity by disrupting tight junctions, adherens junctions, and focal adhesions, leading to leukocyte infiltration and procoagulant signaling.
- Immune cell subsets, including monocytes/macrophages, eosinophils, and lymphoid cells, orchestrate inflammatory responses and mediate ECM breakdown.
- Activated fibroblast subpopulations contribute to fibrotic remodeling and interact closely with smooth muscle cells.
- Advances in single-cell multiomics and lineage-tracing technologies have uncovered novel disease mechanisms and cell-specific therapeutic targets, offering potential for precision medicine in AAD treatment.