Antiangiogenic properties of BthMP, a P–I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cells

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dc.contributorLab. Imunopatologiapt_BR
dc.contributor.authorOliveira, Vinícius Queirozpt_BR
dc.contributor.authorSantos, Luísa Carregosapt_BR
dc.contributor.authorTeixeira, Samuel Cotapt_BR
dc.contributor.authorClissa, Patricia Biancapt_BR
dc.description.abstractAngiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P–I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 μg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 μg/mL, respectively, and the number of tubules by 15.9 at 5 μg/mL and 21.6 at 40 μg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 μg/mL and by 66% at 40 μg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.pt_BR
dc.description.sponsorship(FAPEMIG) Fundação de Amparo à Pesquisa do Estado de Minas Geraispt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.relation.ispartofBiochemical and Biophysical Research Communicationspt_BR
dc.rightsRestricted accesspt_BR
dc.titleAntiangiogenic properties of BthMP, a P–I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cellspt_BR
dc.contributor.external(UFBA) Universidade Federal da Bahiapt_BR
dc.contributor.external(UFU) Universidade Federal de Uberlândiapt_BR
dc.contributor.externalUniversidad del Vallept_BR
dc.subject.keywordsnake venompt_BR
dc.subject.keywordantiangiogenic effects and VEGF pathwaypt_BR
dc.relation.ispartofabbreviatedBiochem Biophys Res Communpt_BR
dc.identifier.citationabntv. 706, 149748, abr. 2024.pt_BR
dc.identifier.citationvancouver2024 Apr; 706:149748pt_BR
dc.contributor.butantanClissa, Patricia Bianca|:Pesquisador|:Lab. Imunopatologiapt_BR
dc.sponsorship.butantan(FAPEMIG) Fundação de Amparo à Pesquisa do Estado de Minas Gerais¦¦APQ-01401-17pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦465669/2014-0pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦001pt_BR
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