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Advisor(s)
Abstract(s)
O Bisfenol A (BPA) é um disruptor endócrino amplamente produzido mundialmente. O
BPA está presente em plásticos policarbonatos e resinas epóxi, usados na produção de
biberões para bebés, recipientes de armazenamento de alimentos e bebidas, materiais
industriais, médicos, entre outros. O BPA possui propriedades estrogénicas e
androgénicas, tendo sido encontrado a sua acumulação em tecidos cerebrais, sendo
posteriormente associado a efeitos prejudiciais a nível neurológico e vascular,
nomeadamente na Acidente Vascular Cerebral (AVC). Este tipo de lesão cerebral afeta
consideravelmente as artérias e vasos sanguíneos, nomeadamente a artéria cerebral
média (MCA), prejudicando a viabilidade das células musculares lisas (SMC). As SMC
desempenham um papel fundamental na regulação do tónus vascular e
consequentemente na integridade vascular e homeostasia cerebral. Neste sentido, este
trabalho pretende analisar os mecanismos pelos quais o BPA altera na função contrátil
das células musculares lisas da artéria cerebral média (SMC-MCA) de rato. Deste modo,
foram isolados explantes da MCA de ratos Wistar e aderidos a placas de culturas
previamente revestidas com colagénio, de modo a obter culturas puras de SMC. A partir
destas culturas foram realizados três ensaios. O ensaio de MTT, de modo a testar a
viabilidade celular, proliferação e citotoxicidade das SMC-MCA em resposta ao BPA. O
ensaio de contractilidade por Planar Cell Surface Area, para analisar a resposta
vasoativa das SMC-MCA em resposta ao agente contrátil, noradrenalina (NA), e ao
agente relaxante, nitroprussiato de sódio (SNP). E em último por Real time-PCR, para
avaliar a expressão das subunidades de canais iónicos e proteínas envolvidas na resposta
contrátil da MCA. Os resultados deste estudo demonstraram que a exposição a BPA pode
modificar a resposta vasorelaxante das SMC-MCA. Os efeitos genómicos dependeram da
concentração de incubação com o BPA, induzindo uma alteração da resposta contrátil,
devido a alterações na expressão da subunidade a do BKCa 1.1, bem como a proteína sGC.
Em suma, estas observações sugerem que a exposição ao BPA altera a homeostasia
vascular da SMC-MCA, podendo estar, por isso, implicado na ocorrência de AVC
isquémico, evidenciando a necessidade urgente de compreender esta ligação e os
mecanismos associados, sendo por isso necessários mais estudos.
Bisphenol A (BPA) is an endocrine-disrupting compound that is widely produced worldwide. BPA is present in polycarbonate plastics and epoxy resins, materials used in the production of baby bottles, food and drink storage containers, and industrial and medical materials, among others. BPA has estrogenic and androgenic properties, and has been found to accumulate in brain tissue, and subsequently associated with harmful effects at a neurological and vascular level, namely in strokes. This type of brain injury considerably affects arteries and blood vessels, particularly the middle cerebral artery (MCA), damaging the viability of smooth muscle cells (SMC). SMC play a fundamental role in regulating vascular tone and consequently vascular integrity and cerebral homeostasis. This study aims to analyse the mechanisms by which BPA alters the contractile function of rat middle cerebral artery smooth muscle cells (SMC-MCA). Thus, explants were isolated from the MCA of Wistar rats and adhered to culture plates previously coated with collagen, in order to obtain pure SMC cultures. Three tests were carried out on these cultures. The MTT assay, to test cell viability, proliferation, and cytotoxicity of SMC-MCA in response to BPA. The contractility assay by Planar Cell Surface Area, to analyse the vasoactive response of SMC-MCA in response to the contractile agent, noradrenaline (NA), and the relaxing agent, sodium nitroprusside (SNP). Finally, Real-time-PCR was used to assess the expression of ion channel subunits and proteins involved in the MCA contractile response. The results of this study showed that exposure to BPA can modify the vasorelaxant response of SMC-MCA. The genomic effects depended on the incubation concentration, inducing an alteration in the contractile response due to changes in the expression of the a subunit of BKCa 1.1, as well as the sGC protein. In short, these observations suggest that exposure to BPA alters the vascular homeostasis of SMC-MCA and may therefore be implicated in the occurrence of ischemic stroke, highlighting the urgent need to understand this involvement and the associated mechanisms, which is why more studies are needed.
Bisphenol A (BPA) is an endocrine-disrupting compound that is widely produced worldwide. BPA is present in polycarbonate plastics and epoxy resins, materials used in the production of baby bottles, food and drink storage containers, and industrial and medical materials, among others. BPA has estrogenic and androgenic properties, and has been found to accumulate in brain tissue, and subsequently associated with harmful effects at a neurological and vascular level, namely in strokes. This type of brain injury considerably affects arteries and blood vessels, particularly the middle cerebral artery (MCA), damaging the viability of smooth muscle cells (SMC). SMC play a fundamental role in regulating vascular tone and consequently vascular integrity and cerebral homeostasis. This study aims to analyse the mechanisms by which BPA alters the contractile function of rat middle cerebral artery smooth muscle cells (SMC-MCA). Thus, explants were isolated from the MCA of Wistar rats and adhered to culture plates previously coated with collagen, in order to obtain pure SMC cultures. Three tests were carried out on these cultures. The MTT assay, to test cell viability, proliferation, and cytotoxicity of SMC-MCA in response to BPA. The contractility assay by Planar Cell Surface Area, to analyse the vasoactive response of SMC-MCA in response to the contractile agent, noradrenaline (NA), and the relaxing agent, sodium nitroprusside (SNP). Finally, Real-time-PCR was used to assess the expression of ion channel subunits and proteins involved in the MCA contractile response. The results of this study showed that exposure to BPA can modify the vasorelaxant response of SMC-MCA. The genomic effects depended on the incubation concentration, inducing an alteration in the contractile response due to changes in the expression of the a subunit of BKCa 1.1, as well as the sGC protein. In short, these observations suggest that exposure to BPA alters the vascular homeostasis of SMC-MCA and may therefore be implicated in the occurrence of ischemic stroke, highlighting the urgent need to understand this involvement and the associated mechanisms, which is why more studies are needed.
Description
Keywords
Acidentevascularcerebral Artériacerebralmédia Bisfenola Célulasmusculareslisas Compostodisruptorendócrino Isquemia Vasoconstrição Vasorelaxamento