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

Abdominal aortic aneurysm (AAA) is a chronic vascular disorder characterized by progressive aortic dilation and extracellular matrix remodeling, for which effective pharmacological therapies remain limited. Fibroblast growth factor 7 (FGF7), a paracrine growth factor involved in tissue repair and remodeling, has not been fully investigated in AAA. Transcriptomic analyses of GSE239620 and GSE57691 revealed dysregulated FGF7 expression in aneurysmal tissues, with predominant localization in fibroblasts. In an Ang II-induced AAA model in Apoe^⁻/⁻ mice, AAV-mediated FGF7 overexpression showed a trend toward improved survival, reduced AAA incidence, limited maximal aortic dilation, and attenuated collagen deposition and inflammatory cytokine production in vivo. In vitro, Ang II stimulation increased FGF7 expression in NIH/3T3 fibroblasts. Recombinant FGF7 suppressed Ang II-induced upregulation of Collagen I, α-SMA, MMP-2, and MMP-9. Mechanistically, Ang II activated PI3K/AKT signaling, whereas FGF7 further enhanced PI3K and AKT phosphorylation. Pharmacological inhibition of PI3K partially abolished the regulatory effects of FGF7 on fibroblast remodeling and inflammatory activation. Collectively, FGF7 mitigates AAA progression through modulation of fibroblast-mediated extracellular matrix remodeling and PI3K/AKT signaling, highlighting its potential as a therapeutic target for AAA.