From venom to vasculature: exploring how snake VEGFs influence vascular and lymphatic endothelial biology

Snake venom vascular endothelial growth factors (svVEGFs) constitute a unique toxin class that selectively engage VEGF receptors, thereby driving vascular permeability, endothelial activation, and hypotension. Whilst their vascular effects are well documented, their impact on lymphatic biology remains largely unexplored. Here, we integrate current knowledge of svVEGFs, from structural diversity and receptor specificity to signalling cascades, highlighting parallels and differences with human VEGFs. Based on the available evidence, we propose a conceptual dual-system pathophysiological model of snake envenomation that incorporates the coordinated roles of the vascular and lymphatic systems in venom dissemination and pathogenesis, with svVEGFs as one venom component that may modulate these processes by acting on both blood and lymphatic endothelium. This perspective underscores the need to further investigate svVEGF-lymphatic interactions to refine our understanding of snake envenomation and to identify novel molecular tools and potential therapeutic targets.