2. Academic Validation
  3. Periaortic lymphatic vessels protect against thoracic aortic dissection through mobilizing immune response

Periaortic lymphatic vessels protect against thoracic aortic dissection through mobilizing immune response

  • Cardiovasc Res. 2025 Dec 18;121(16):2594-2609. doi: 10.1093/cvr/cvaf215.
Yujun Pei 1,  Weirui Lin 2,  Tao Zhang 3,  Xiangyu Chu 3,  Han Xu 1,  Yizhe Sun 4,  Min Xu 2,  Yanjiani Xu 5 6,  Fangyang Huang 5 6,  Di Huang 7,  Liang Shi 7,  Hu Zhao 8,  Mingzhao Li 8 9,  Dangfeng Zhao 10 11,  Hongjia Zhang 12 13 14 15,  Wenjian Jiang 12 13 14 15,  Mao Chen 5 6,  Jincai Luo 1,  Changping Zhou 2
Affiliations

Affiliations

  • 1 Laboratory of Vascular Biology, Institute of Molecular Medicine, School of Future Technology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, No. 5 Yiheyuan Road, Haidian District, Beijing 100871, China.
  • 2 Center for Stem Cell and Regenerative Medicine, Institute of Blood Transfusion, Chinese Academy of Medical Sciences/Peking Union Medical College, No. 76 Huacai Road, Chenghua District, Chengdu, Sichuan 610052, China.
  • 3 Department of Vascular Surgery, Peking University People's Hospital, Beijing 100044, China.
  • 4 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm 17177, Sweden.
  • 5 Department of Cardiology, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 6 Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 7 Light Innovation Technology Ltd., Shenzhen 518109, China.
  • 8 Chinese Institute for Brain Research, Changping District, Beijing 102206, China.
  • 9 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
  • 10 Henan Medical School, Henan University, Kaifeng City, Henan 475004, China.
  • 11 Yongkang Liande Hospital of Traditional Chinese Medicine, Yongkang City, Jinhua City, Zhejiang 321302, China.
  • 12 Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
  • 13 Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
  • 14 Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China.
  • 15 Beijing Lab for Cardiovascular Precision Medicine, Capital Medical University, Beijing 100069, China.
PMID: 41213294 DOI: 10.1093/cvr/cvaf215
Abstract

Aims: Inflammation and the immune response are crucial factors in the progression of thoracic aortic dissection (TAD), while lymphatic vessels (LVs) play a key role in regulating the inflammatory response by facilitating the drainage of inflammatory mediators, and immune cell trafficking. Here, we investigated the role of LVs in the pathogenesis of TAD.

Methods and results: Aortas collected from TAD patients and mice both showed a reduction in the number of periaortic LVs during TAD progression. Genetic linage tracing, tissue clearing technology, and fluorochrome tracers were used to explore the draining lymph nodes (LNs) of the aorta. The results demonstrated that the tracheobronchial lymph node (TLN) was the primary draining LN for the thoracic aorta. Besides, we further found that the drainage of periaortic LVs was decreased and the immune cell population in the TLN was changed in TAD. Then, lymphatic-deficient models, including genetic ablation and TLN removal, indicated that lymphatic deficiency exacerbated TAD. Furthermore, enhancing lymphangiogenesis with hVEGF-C156S treatment inhibited TAD depended on an intact lymphatic system. Mechanistically, single-cell RNA Sequencing analysis showed that lymphatic endothelial cells (LECs) recruited immune cells by CXCL12-CXCR4 signalling in TAD. Importantly, blockade of CXCR4 by AMD3100 abolished the protective role of hVEGF-C156S in TAD, revealing that periaortic LVs protected against TAD progression via CXCL12-CXCR4 signalling. Finally, single-cell RNA Sequencing analysis of human TAD tissue confirmed that LEC-induced immune cell recruitment played a key role in TAD.

Conclusion: Our findings demonstrated that the TLN and associated periaortic LVs form a functional lymphatic system, which drains the thoracic aorta and plays an inhibitory role in TAD progression, indicating that enhancing lymphatic function may represent a potential therapeutic strategy for treating TAD.

Keywords

Aortic dissection; CXCR4; Draining lymph nodes; Lymphatic vessels; VEGF-C156S.

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