Scholarlink

Background <p>Abdominal aortic aneurysm (AAA) has an 80% mortality rate upon rupture, with no pharmacological treatments available to slow its progression. Hydrogen sulfide (H₂S), produced by cystathionine γ-lyase (CSE), has anti-inflammatory and antioxidant properties, but its role in AAA remains unclear.</p> Methods <p>We evaluated the impact of sodium thiosulfate (STS), a clinically relevant H₂S donor, in a periadventitial elastase-induced AAA model in normotensive male wild-type and Cse<sup>−/−</sup> mice. Complementary in vitro studies were conducted on primary human vascular smooth muscle cells (VSMCs) to assess the effects of STS on proliferation, senescence and cytokine-induced apoptosis.</p> Results <p>Contrary to expectations, STS dose-dependently aggravate AAA progression by increasing extracellular matrix degradation. Although STS reduces macrophage and lymphocyte infiltration, it enhances neutrophil accumulation, particularly MMP9⁺ neutrophils, and promotes the formation of c-KIT⁺-MPO⁺ pre-neutrophil clusters. Cse<sup>−/−</sup> mice show reduced neutrophil infiltration and smaller aneurysms, supporting a pathogenic role of endogenous H₂S. STS also impairs VSMC proliferation and induces senescence, blunting compensatory aortic remodeling.</p> Conclusions <p>H₂S, delivered via STS, exacerbates AAA progression under normotensive conditions by promoting neutrophil-driven inflammation and impairing VSMC repair. These findings challenge the assumption that H₂S is universally protective in vascular disease and raise caution regarding the therapeutic use of STS in patients at risk for AAA.</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

Hydrogen sulfide aggravates neutrophil infiltration, vascular remodeling and elastase-induced abdominal aortic aneurysm in male mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Clémence Bechelli,
  • Diane Macabrey,
  • Florian Caloz,
  • Severine Urfer,
  • Martine Lambelet,
  • Florent Allagnat,
  • Sébastien Déglise

摘要

Background

Abdominal aortic aneurysm (AAA) has an 80% mortality rate upon rupture, with no pharmacological treatments available to slow its progression. Hydrogen sulfide (H₂S), produced by cystathionine γ-lyase (CSE), has anti-inflammatory and antioxidant properties, but its role in AAA remains unclear.

Methods

We evaluated the impact of sodium thiosulfate (STS), a clinically relevant H₂S donor, in a periadventitial elastase-induced AAA model in normotensive male wild-type and Cse−/− mice. Complementary in vitro studies were conducted on primary human vascular smooth muscle cells (VSMCs) to assess the effects of STS on proliferation, senescence and cytokine-induced apoptosis.

Results

Contrary to expectations, STS dose-dependently aggravate AAA progression by increasing extracellular matrix degradation. Although STS reduces macrophage and lymphocyte infiltration, it enhances neutrophil accumulation, particularly MMP9⁺ neutrophils, and promotes the formation of c-KIT⁺-MPO⁺ pre-neutrophil clusters. Cse−/− mice show reduced neutrophil infiltration and smaller aneurysms, supporting a pathogenic role of endogenous H₂S. STS also impairs VSMC proliferation and induces senescence, blunting compensatory aortic remodeling.

Conclusions

H₂S, delivered via STS, exacerbates AAA progression under normotensive conditions by promoting neutrophil-driven inflammation and impairing VSMC repair. These findings challenge the assumption that H₂S is universally protective in vascular disease and raise caution regarding the therapeutic use of STS in patients at risk for AAA.