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

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Aortic Disease Research

Background:

• Abdominal aortic aneurysm (AAA) is a serious condition lacking effective drug treatments.
• Growth Differentiation Factor 11 (GDF11), a TGF-β superfamily member, is implicated in cardiovascular health.
• Reduced GDF11 expression is observed in AAA tissues, decreasing with disease advancement.

Purpose of the Study:

• To investigate the role of GDF11 in the pathogenesis of abdominal aortic aneurysm.
• To explore GDF11's therapeutic potential for mitigating AAA progression.

Main Methods:

• Transcriptomic analysis of AAA tissues (GSE57691) to assess GDF11 expression.
• Utilized an Angiotensin II-induced AAA mouse model (ApoE-/-) to study GDF11's effects.
• Employed Adeno-Associated Virus (AAV)-mediated GDF11 gene delivery for therapeutic intervention.
• Conducted in vitro experiments on vascular smooth muscle cells (VSMCs) to elucidate molecular mechanisms.

Main Results:

• GDF11 expression was significantly reduced in AAA tissues and negatively correlated with inflammatory markers (IL-1β, IL-6) and matrix metalloproteinases (MMP-2, MMP-9).
• GDF11 overexpression in mice reduced AAA incidence, limited aortic dilation, and attenuated matrix degradation and inflammation.
• GDF11 inhibited inflammatory cytokines, preserved extracellular matrix integrity, and maintained VSMC phenotype via TGF-β/Smad2/3 signaling.

Conclusions:

• GDF11 plays a protective role against AAA development and progression.
• GDF11 mitigates AAA by suppressing inflammation, preserving extracellular matrix, and maintaining VSMC function through TGF-β/Smad2/3 signaling.
• GDF11 represents a potential therapeutic target for abdominal aortic aneurysm.