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Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in different diseases. This study aimed to identify proteins in peritoneal exudate and plasma EVs isolated from BALB/c mice following a 30 min post-injection of Crotalus scutulatus scutulatus venom and its purified CRiSP (Css-CRiSP). EVs were isolated from these biofluids using the EVtrap method. Proteomic analysis of exudate- and plasma-derived EVs was performed using LC-MS/MS. We observed significant upregulation or downregulation of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. These findings suggest that svCRiSPs play a crucial role in the acute effects of venom and contribute to the local and systemic toxicity of snakebites. Key Contribution: This study reveals the immediate effects of crotaline CRiSP and crude venom by exploring the proteomic profile of peritoneal exudate- and plasma-derived EVs in mice injected with Css-CRiSP and C. s. scutulatus crude venom. Using the proteomic profile of exudate- and plasma-derived EVs provides a more comprehensive understanding of the pathophysiology of snakebites and allows for more precise targeting of therapeutic interventions. In addition, such profiling could also help identify novel biomarkers useful in predicting symptoms and progression of snakebite complications and facilitating the development of new treatments.


© 2023 by the authors.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title



10.3390/ toxins15070434

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Mentor/PI Department

Office of Human Genetics



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