VEGFAs

VEGFAs refers to the VEGFA gene and its family of isoforms, which encode vascular endothelial growth factor A, a key signaling protein in angiogenesis and vascular biology. VEGFA is produced in multiple mRNA splice variants, resulting in a set of protein isoforms with distinct properties, tissue distributions, and receptor interactions. Pro-angiogenic isoforms generally promote blood vessel formation, while anti-angiogenic isoforms such as VEGF-A165b can counteract these effects.

VEGFA signals primarily through receptor tyrosine kinases on endothelial cells. The main receptors are VEGF receptors 1 and 2 (VEGFR-1/FLT1 and VEGFR-2/KDR/FLK1). Neuropilins (NRP1 and NRP2) act as co-receptors that modulate signaling. Binding of VEGFA to these receptors activates downstream pathways, including Ras–Raf–MEK–ERK, PI3K–Akt, and PLCγ, leading to endothelial cell proliferation, migration, and changes in vascular permeability.

Physiological roles of VEGFA include vascular development during embryogenesis, placental and reproductive processes, and tissue remodeling such as wound healing. It also regulates permeability in various tissues, including the retina, where tight control is important for normal function.

Dysregulation of VEGFA contributes to pathology. Pathological angiogenesis supports tumor growth and metastasis, and abnormal retinal or choroidal neovascularization occurs in diseases like age-related macular degeneration and diabetic retinopathy. Inflammatory conditions can also involve VEGFA signaling.

Therapeutically, anti-VEGFA strategies aim to inhibit pathological angiogenesis. Agents such as monoclonal antibodies and fusion proteins are used in cancer and ocular diseases, with potential adverse effects including hypertension, thromboembolism, wound-healing impairment, and ocular inflammation. Regulation of VEGFA expression is responsive to hypoxia via hypoxia-inducible factors and various cytokines. The VEGFA gene was identified in the late 1980s as a central mediator of angiogenesis.