Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom

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Ferreira, Isabela ; Oliveira, Isadora ; Bordon, Karla ; Reis, Mouzarllem ; Wiezel, Gisele ; Sanchez, Caroline ; Santos, Luisa ; Santos-Filho, Norival ; Pucca, Manuela ; Antunes, Lusania ; Lopes, Daiana ; Arantes, Eliane

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 15, n. 8, p. 21-pg., 2023-08-01.

Resumo

A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different chromatographic steps, representing 2% of soluble venom proteins. Its primary sequence was determined using mass spectrometry analysis, and the molecule demonstrated no affinity to heparin. The Brazilian crotalid antivenom recognized CdtVEGF. Both native and PEGylated CdtVEGF were able to induce new vessel formation and migration, and to increase the metabolic activity of human umbilical endothelial vascular cells (HUVEC), resulting in better wound closure (similar to 50% within 12 h) using the native form. CdtVEGF induced leukocyte recruitment to the peritoneal cavity in mice, with a predominance of neutrophil influx followed by lymphocytes, demonstrating the ability to activate the immune system. The molecule also induced a dose-dependent increase in vascular permeability, and PEG-CdtVEGF showed less in vivo inflammatory activity than CdtVEGF. By unraveling the intricate properties of minor components of snake venom like svVEGF, this study illuminates the indispensable significance of exploring these molecular tools to unveil physiological and pathological processes, elucidates the mechanisms of snakebite envenomings, and could possibly be used to design a therapeutic drug. (AU)

• Processo FAPESP: 20/13176-3 - Descoberta de anticorpos monoclonais humanos (scFv) com reatividade cruzada e pH-dependentes para as metaloproteases de Bothrops spp
• Beneficiário: Isadora Sousa de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/11936-3 - Centro de Ciência Translacional e Desenvolvimento de Biofármacos
• Beneficiário: Benedito Barraviera
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Ciência para o Desenvolvimento
• Processo FAPESP: 17/00586-6 - Caracterização de um inibidor de fosfolipase A2 da glândula de peçonha de Crotalus durissus terrificus: um possível adjuvante na terapia do envenenamento
• Beneficiário: Gisele Adriano Wiezel
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/10173-6 - Produção, modificação e caracterização de toxinas animais com potencial aplicação biotecnológica
• Beneficiário: Eliane Candiani Arantes Braga
• Modalidade de apoio: Auxílio à Pesquisa - Regular