Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2026年2月27日

查看全文
  • Mei-Hua Chen,
  • Yi-Jie Hua,
  • Yan Li,
  • Yu Lei,
  • Si-Yuan Zhou,
  • Xi-De Hu,
  • Dong-Hua Hu,
  • Zhi-Hui Dong,
  • Yan Lu,
  • Tao Zhuang,
  • Cheng-Chao Ruan

摘要

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.