2. Academic Validation
  3. Sparcl1 mitigates abdominal aortic aneurysm through inhibiting lymphangiogenesis-mediated TLS formation

Sparcl1 mitigates abdominal aortic aneurysm through inhibiting lymphangiogenesis-mediated TLS formation

  • Nat Immunol. 2026 Apr;27(4):738-749. doi: 10.1038/s41590-026-02454-1.
Mei-Hua Chen # 1,  Yi-Jie Hua # 2,  Yan Li 3,  Yu Lei 2,  Si-Yuan Zhou 4,  Xi-De Hu 2,  Dong-Hua Hu 2,  Zhi-Hui Dong 5,  Yan Lu 6,  Tao Zhuang 7,  Cheng-Chao Ruan 8 9
Affiliations

Affiliations

  • 1 Institute of Metabolism and Regenerative Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 3 Department of Cardiology, RuiJin Hospital/LuWan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 4 Department of Vascular Surgery, Zhongshan Hospital, and Center for Vascular Surgery and Wound Care, Jinshan Hospital, Fudan University, Shanghai, China.
  • 5 Department of Vascular Surgery, Zhongshan Hospital, and Center for Vascular Surgery and Wound Care, Jinshan Hospital, Fudan University, Shanghai, China. [email protected].
  • 6 Institute of Metabolism and Regenerative Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 7 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China. [email protected].
  • 8 Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. [email protected].
  • 9 Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 41760906 DOI: 10.1038/s41590-026-02454-1
Abstract

Vascular tissue-resident macrophages (VRMs) maintain immune balance in blood vessels, but their role in abdominal aortic aneurysm (AAA) development remains unclear. Here we demonstrated that a specific group of VRMs located in the adventitia marked by expression of Lyve1, protected against AAA by secreting the extracellular matrix protein Sparcl1 (Sc1). Deletion of Sc1 in VRMs promoted dysfunctional lymphangiogenesis and led to the formation of tertiary lymphoid structures (TLSs), thereby accelerating AAA progression. Mechanistically, the calcium-binding domain of Sc1 acted as a trap for the growth factor FGF2, inhibiting FGF2-mediated dysfunctional lymphangiogenesis and expression of genes associated with TLS formation. A therapeutic peptide derived from Sc1 (Spa17) mitigated AAA progression in several AAA models. Our findings reveal that VRM-derived Sc1 has a protective role in AAA and identify a potential therapeutic approach.

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