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<p>Abdominal aortic aneurysm (AAA) is a chronic aortic disease that currently lacks effective pharmacological treatments. Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. Transcriptomic analysis of GSE57691 revealed significantly reduced GDF11 expression in AAA tissues, with further decline from early- to advanced-stage disease. GDF11 levels correlated negatively with IL-1β, IL-6, MMP-2, and MMP-9, and positively with ACTA2 and TGF-β/Smad2/3 signaling. In an Ang II-induced AAA model of ApoE<sup>−/−</sup> mice, GDF11 was markedly decreased, accompanied by inflammation, matrix degradation, and vascular remodeling. AAV-mediated GDF11 overexpression improved survival, reduced AAA incidence, limited aortic dilation, and attenuated elastin degradation and collagen deposition. Mechanistically, GDF11 inhibited inflammatory cytokines, downregulated MMP-2/9, restored ACTA2, and modulated TGF-β/Smad2/3 signaling. In vitro, GDF11 attenuated Ang II-induced phenotypic switching of vascular smooth muscle cells (VSMCs), while inhibition of TGF-β/Smad2/3 signaling reversed these effects. In conclusion, GDF11 mitigates AAA progression by suppressing inflammation, preserving extracellular matrix integrity, and maintaining VSMC phenotype via TGF-β/Smad2/3 signaling, highlighting its potential as a therapeutic target for AAA.</p>

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GDF11 Regulates Vascular Smooth Muscle Cell Phenotype Switching to Prevent Aortic Aneurysm Formation

  • 期刊论文

  • 发表日期：

    2025年11月15日

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  • Xiang Su,
  • Lulu Chen,
  • Yihui Qiu,
  • Yajing Yang,
  • Bicheng Chen

摘要

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that currently lacks effective pharmacological treatments. Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. Transcriptomic analysis of GSE57691 revealed significantly reduced GDF11 expression in AAA tissues, with further decline from early- to advanced-stage disease. GDF11 levels correlated negatively with IL-1β, IL-6, MMP-2, and MMP-9, and positively with ACTA2 and TGF-β/Smad2/3 signaling. In an Ang II-induced AAA model of ApoE−/− mice, GDF11 was markedly decreased, accompanied by inflammation, matrix degradation, and vascular remodeling. AAV-mediated GDF11 overexpression improved survival, reduced AAA incidence, limited aortic dilation, and attenuated elastin degradation and collagen deposition. Mechanistically, GDF11 inhibited inflammatory cytokines, downregulated MMP-2/9, restored ACTA2, and modulated TGF-β/Smad2/3 signaling. In vitro, GDF11 attenuated Ang II-induced phenotypic switching of vascular smooth muscle cells (VSMCs), while inhibition of TGF-β/Smad2/3 signaling reversed these effects. In conclusion, GDF11 mitigates AAA progression by suppressing inflammation, preserving extracellular matrix integrity, and maintaining VSMC phenotype via TGF-β/Smad2/3 signaling, highlighting its potential as a therapeutic target for AAA.