Integrated Single‐Cell and Spatial Analysis Reveals a Metabolic‐Immune Axis Driving Aortic Dissection
Although single-cell studies have profiled diseased aorta, mechanisms driving aortic dissection (AD) remain largely elusive owing to limited cohorts. Here, we integrate single-cell and spatial transcriptomic data from 110 thoracic aortic samples (80 individuals; control, aneurysm, dissection; 767 018 high-quality cells) to generate a comprehensive thoracic-aorta cellular-molecular atlas. We identify an elastin-rich fibroblast subset (Fibro_C1_FBN1+; FBN1, MFAP5, LOX) that declines with age and is markedly depleted in AD, linking fibroblast loss to increased aortic wall vulnerability and dissection risk. Vascular smooth muscle cells (vSMCs) undergo ENO1-driven glycolytic reprogramming under hypoxia, lose contractility and adopt a synthetic, MIF-secreting phenotype that engages macrophage receptors to promote macrophage recruitment and pro-inflammatory polarization, leading aggregated macrophages to upregulate proteolytic and fibrinolytic pathways and thereby accelerate extracellular-matrix degradation. In vitro and in vivo, ENO1 knockdown inhibits vSMC switching, reduces macrophage inflammation, and slows AD progression. This stromal-immune axis suggests potential therapeutic targets in AD.
Authors
- Yi Yang (ORCID: https://orcid.org/0000-0002-4091-8532)
- Fan Yang (ORCID: https://orcid.org/0000-0002-1044-7821)
- X Chen
- Zhimin Yang (ORCID: https://orcid.org/0009-0009-7549-3456)
- Yue Wang (ORCID: https://orcid.org/0000-0001-6636-354X)
- Xiaodong Fang (ORCID: https://orcid.org/0000-0001-7061-3337)
- Jiahui Yong (ORCID: https://orcid.org/0000-0001-7668-2325)
- Juan Shen (ORCID: https://orcid.org/0000-0001-5048-3838)
- R Y Chen (ORCID: https://orcid.org/0009-0006-9946-966X)
- Huanjie Yang (ORCID: https://orcid.org/0000-0002-2424-4937)
- Zhensheng Dong
- Hui Peng
- Yi-Xiang Wang (ORCID: https://orcid.org/0000-0002-4021-4228)
- Zijie Wang (ORCID: https://orcid.org/0009-0005-2860-6244)
- Yang Chen
- Li Pang
- Xueli Wu
- Lei Yan
- Karsten Kristiansen
- Fan Luo
- Shanshan Pan
- Deyang Li
- Mengjun Yu
- Qiang Zhao
- Hongjian Zheng
- Jing Tao (ORCID: https://orcid.org/0000-0002-8438-3349)
Institutions
- BGI Group (China) (CN)
- Guangzhou University of Chinese Medicine (CN)
- Beijing Graphene Institute (CN)
- People's Hospital of Xinjiang Uygur Autonomous Region (CN)
- Shandong Eye Institute & Hospital (CN)
- Sanya Central Hospital (CN)
- Sanya University (CN)
- University of Chinese Academy of Sciences (CN)
- Zhuhai Institute of Advanced Technology (CN)
- BGI Research (CN)
- IT University of Copenhagen (DK)
- Xinjiang University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2026-05-10
- DOI
- https://doi.org/10.1002/advs.75509
- Primary Topic
- Connective tissue disorders research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China