VEGFää

VEGFää, commonly written as VEGFα, is a member of the vascular endothelial growth factor (VEGF) family. It encodes a secreted glycoprotein that promotes angiogenesis and increases vascular permeability, playing a central role in development, wound healing, and tissue regeneration. As a dimer, VEGFää interacts with receptor tyrosine kinases on endothelial cells, activating signaling pathways that drive blood vessel formation and maintenance.

VEGFää signals primarily through VEGF receptors, especially VEGFR-2 (KDR/Flk-1), with VEGFR-1 (FLT1) modulating the response. Co-receptors such as neuropilins (NRP-1 and NRP-2) enhance ligand binding and specificity. Receptor activation triggers intracellular cascades, including the PI3K/Akt, MAPK/ERK, and PLCγ pathways, which promote endothelial cell proliferation, migration, and survival. The extracellular matrix and heparan sulfate proteoglycans influence VEGFää presentation and diffusion, shaping angiogenic gradients.

Expression and regulation: VEGFää expression is upregulated by hypoxia through hypoxia-inducible factors (notably HIF-1α). It is produced by a variety of cells, including endothelial cells, tumor cells, macrophages, and adipocytes. Alternative splicing generates multiple isoforms with distinct diffusibility and receptor-binding properties, allowing fine-tuning of angiogenic signaling in different tissues.

Physiological and pathological roles: VEGFää is essential for vasculogenesis and the repair of damaged vasculature. Dysregulation contributes to diseases characterized by abnormal angiogenesis, such as cancer, diabetic retinopathy, and age-related macular degeneration. Clinically, VEGF pathway inhibitors (antibodies, decoy receptors, or receptor TKIs) are used to treat cancer and ocular neovascular disorders, illustrating the therapeutic relevance of VEGFα activity.