Angiogenesis, the formation of new blood vessels, plays a critical role in various physiological and pathological conditions. Snake venom disintegrins (SVDs) have been identified as significant regulators of this process. In this review, we explore the dual roles of SVD in angiogenesis, both as antiangiogenic agents by inhibiting integrin binding and interfering with vascular endothelial growth factors and as proangiogenic agents by enhancing integrin binding, stimulating cell migration and proliferation, and inducing neoangiogenesis. Studies in vitro and in animal models have demonstrated these effects and offer significant therapeutic opportunities. The potential applications of SVD in diseases related to angiogenesis, such as cancer, ocular diseases, tissue regeneration, wound healing, and cardiovascular diseases, are also discussed. Overall, SVDs are promising potential therapeutics, and further advances in this field could lead to innovative treatments for diseases related to angiogenesis.

Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of different SVMPs domains in inducing the expression of adhesion molecules at the microcirculation of the cremaster muscle of mice. We used Jararhagin (Jar)—a PIII SVMP with intense hemorrhagic activity, and Jar-C—a Jar devoid of the catalytic domain, with no hemorrhagic activity, both isolated from B. jararaca venom and BnP-1—a weakly hemorrhagic P1 SVMP from B. neuwiedi venom. Toxins (0.5 µg) or PBS (100 µL) were injected into the scrotum of mice, and 2, 4, or 24 h later, the protein and gene expression of CD54 and CD31 in the endothelium, and integrins (CD11a and CD11b), expressed in leukocytes were evaluated. Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment.

Patagonfibrase is a P-III class metalloproteinase isolated from the venom of Philodryas patagoniensis, a South-American, rear-fanged ‘colubrid’ snake responsible for accidents with clinical significance. Since local inflammatory reactions are conspicuous signs of snakebites inflicted by this species and taking into consideration that most snake venom metalloproteinases exhibit inflammatory activity, this study deals with the proinflammatory effects evoked by patagonfibrase. Herein, we demonstrate that patagonfibrase causes a time- and dose-dependent hemorrhagic edema when injected into mouse hind paws. The peak of edema occurred at 30 min after injection, and the minimum edematogenic dose was 0.021 μg. By histological analysis, the presence of moderate to marked edema and hemorrhage, and a mild inflammatory infiltrate was observed. When injected subcutaneously into the scrotal bag of mice, patagonfibrase induced cell recruitment with a significant alteration in physiological parameters of leukocyte–endothelium interaction. The presence of 1 mmol/L o-phenanthroline, which chelates metal ions, significantly inhibited the proinflammatory effects induced by patagonfibrase. Taken together, these results imply that patagonfibrase is an important contributor to local inflammation elicited by P. patagoniensis envenomation, which may pave the way for novel therapeutic strategies to treat this snakebite. Moreover, our findings demonstrate for the first time that a venom metalloproteinase from a rear-fanged snake elicits proinflammatory effects mainly mediated by its catalytic activity.