Fibroblast Growth Factor 7 Limits Fibroblast-Driven Matrix Remodeling in Abdominal Aortic Aneurysm

Area of Science:

• Vascular Biology
• Extracellular Matrix Remodeling
• Fibroblast Signaling

Background:

• Abdominal aortic aneurysm (AAA) is a vascular disorder with limited pharmacological treatments.
• Fibroblast growth factor 7 (FGF7) role in AAA pathogenesis is not fully understood.
• Transcriptomic data indicates dysregulated FGF7 expression in aneurysmal tissues.

Purpose of the Study:

• Investigate the role of FGF7 in AAA.
• Determine FGF7's therapeutic potential for AAA.

Main Methods:

• Analysis of transcriptomic datasets (GSE239620, GSE57691).
• In vivo studies using Angiotensin II-induced AAA model in Apoe knockout mice with AAV-mediated FGF7 overexpression.
• In vitro studies using NIH/3T3 fibroblasts stimulated with Angiotensin II and treated with recombinant FGF7.
• Assessment of PI3K/AKT signaling pathway activation.

Main Results:

• FGF7 expression is altered in AAA tissues, primarily in fibroblasts.
• FGF7 overexpression in vivo demonstrated trends toward improved survival, reduced AAA incidence, and attenuated pathological features.
• In vitro, FGF7 suppressed Ang II-induced upregulation of extracellular matrix proteins and matrix metalloproteinases.
• FGF7 enhanced PI3K/AKT signaling, and PI3K inhibition partially reversed FGF7's protective effects.

Conclusions:

• FGF7 mitigates AAA progression by modulating fibroblast-mediated extracellular matrix remodeling.
• FGF7 exerts its effects via the PI3K/AKT signaling pathway.
• FGF7 represents a potential therapeutic target for abdominal aortic aneurysm.