VEGF165a and VEGF165b: Molecular effects of opposing isoforms in angiogenesis

Authors : Funda Çimen Açıkgül, Seçil Nazife Parlak

Pages : 147-155

Doi:10.61845/agrimedical.1684066

View : 90 | Download : 593

Publication Date : 2025-10-29

Article Type : Review Paper

Abstract :This review aims to comparatively examine the structural differences, receptor interactions, downstream signaling effects, and pathophysiological roles of the two main isoforms of the VEGFA gene, VEGF165a and VEGF165b, which arise from alternative splicing of exon 8. Recent experimental and clinical studies conducted between 2020 and 2025 in both human and animal models were systematically reviewed to evaluate the biological functions, receptor-binding properties, and pro- and anti-angiogenic effects of VEGF165b. VEGF165a promotes endothelial cell proliferation, migration, and vascular permeability by activating VEGFR-2 through PI3K/Akt and MAPK/ERK pathways. In contrast, VEGF165b binds to the same receptors but induces weak signaling and competitively inhibits the effects of VEGF165a. While VEGF165b is predominantly expressed in healthy tissues, a shift in favor of VEGF165a is observed in pathological conditions such as cancer, proliferative diabetic retinopathy, and age-related macular degeneration. Conversely, excessive VEGF165b expression is associated with impaired angiogenesis in diseases such as peripheral artery disease, systemic sclerosis, and preeclampsia. Disruption in the VEGF165 isoform balance underlies many diseases characterized by either excessive or insufficient angiogenesis. In this context, isoform-specific therapeutic strategies—such as the modulation of alternative exon usage via splice-switching oligonucleotides—may allow the development of more precise and targeted vascular therapies in the future. The VEGF165a/VEGF165b ratio also holds promise as a biomarker for guiding personalized angiogenesis-modulating treatments.
Keywords : Anjiyogenez, Alternatif dizi birleştirme, İzoformlar, Vasküler endotelyal büyüme faktörü A, VEGFR-2 reseptörü, Sinyal iletimi

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