Erosion or Explosion: Integrated Single-Cell Transcriptomics Reveals Cellular Heterogeneity in Aortic Aneurysm and
Heng Wang1,2, Keyi Fan3,4, Yaling Li5
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Inflammation
|May 12, 2026
Summary
Aortic aneurysm and dissection involve cell loss and immune cell increase. Macrophages drive vascular cell changes via specific signaling pathways, impacting disease progression and rupture.
Area of Science:
- Cardiovascular Biology
- Vascular Cell Biology
- Disease Mechanisms
Background:
- Aortic aneurysm (AA) and aortic dissection (AD) are severe vascular conditions with poorly understood cellular mechanisms.
- Progressive wall degeneration and structural failure characterize these life-threatening diseases.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying aortic aneurysm and dissection progression and rupture.
- To identify disease-specific cellular patterns and signaling pathways involved in AA and AD.
Main Methods:
- Integrative single-cell RNA sequencing analysis of four human aortic datasets (TAD, TAA, AAA, ruptured AAA).
- Analysis of cell-cell communication and identification of key signaling axes and transcription factors.
- Validation in AD mouse models.
Main Results:
- Disease-specific immune cell infiltration and vascular structural cell loss patterns were identified.
- Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) showed reduced numbers in AA and increased numbers in AD.
- Macrophages were found to communicate with VSMCs and ECs via CXCL, IL1B, and SPP1 signaling, activating REL-driven programs.
Conclusions:
- This study reveals distinct cellular heterogeneity and injury mechanisms in AA and AD.
- Inflammatory macrophages play a crucial role in VSMC and EC phenotypic switching, compromising vascular integrity.
- Findings offer potential therapeutic targets for preventing aortic disease progression and rupture.
