Exploring the antiangiogenic effects of Phospholipases A2 from Bothrops diporus venom.

Abstract

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a crucial process in both physiological and pathological contexts, including cancer. Phospholipases A₂ (PLA₂s), enzymes found in snake venoms, have attracted attention due to their potential antiangiogenic properties. In this study, we explored the antiangiogenic effects of PLA₂ isoforms isolated from Bothrops diporus venom using a combination of in vivo and ex vivo models. The chorioallantoic membrane (CAM) assay revealed a significant reduction in vascular density and branching following PLA₂s treatment, with histological analysis confirming vascular regression, including vessel wall thinning and luminal collapse. Moreover, PLA₂s induced endothelial cell apoptosis, as shown by TUNEL staining, and reduced VEGF expression. The filter paper disc variant of the CAM assay further supported these findings, demonstrating inhibited neovascularization while preserving mature vessels. Additionally, the CAM explant assay showed a marked decrease in vascular complexity and branching. These results demonstrate the antiangiogenic effect of PLA₂ isoforms from B. diporus and suggest that these enzymes may modulate key angiogenic pathways. Based on our previous findings, this modulation may involve interference with integrin-mediated signaling, which could underlie the vascular effects observed. Thus, this work provides compelling evidence for the potential role of snake venom-derived PLA₂s in modulating angiogenesis and highlights the need for further research into their mechanisms and possible biomedical applications.