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Authors
Abstract(s)
As doenças cardiovasculares (CVD) representam a causa número um de morte em todo o
mundo. O endotélio vascular pode exercer um papel na fisiopatologia de doenças CVD. O
octilmetoxicinamato (OMC) é um filtro UV-B amplamente usado a nível mundial em
inúmeros produtos de cuidados pessoais, nomeadamente em protetores solares, cremes
diários e maquilhagem. Atualmente o OMC é considerado um disruptor endócrino.
Deste modo, o objetivo desta investigação foi avaliar os efeitos diretos do
Octilmetoxicinamato (OMC) em artérias umbilicais humanas com endotélio, e os possíveis
mecanismos envolvidos na resposta. Para isso foram definidos objetivos específicos: 1.
Realização do isolamento e cultura de células endoteliais da artéria umbilical humana
(HUA) e da veia umbilical humana (HUV); 2. Análise do efeito direto do OMC em HUA
com e sem endotélio; 3. Análise dos possíveis mecanismos envolvidos no efeito do OMC na
HUA com endotélio, principalmente o efeito nas vias de sinalização do óxido Nítrico (NO)
e da Cicloxigenases (COXs) 4. Análise computacional de interação do OMC com proteínas
envolvidas nas vias de sinalização endotelial.
Os resultados demonstraram que o OMC exerce um efeito relaxante arterial rápido (não
genómico) e dependente do endotélio quando as HUA estão previamente contraídas com
serotonina (5-HT) e histamina (Hist). A relaxação nestas artérias foi mais pronunciada na
presença de endotélio, do que na ausência do mesmo, e em HUA contraídas com Hist. Por
outro lado, quando as HUA foram contraídas com cloreto de potássio (KCl) esse efeito
relaxante apenas foi observado nas HUA sem endotélio, parecendo o mesmo estar inibido
nas HUA com o endotélio intacto. Desta forma, o efeito vasorelaxante do OMC não só
depende do endotélio, como mostrou ser dependente do agente contráctil utilizado,
sugerindo que o OMC pode atuar por vias de sinalização diferentes. Assim, quando as
HUA são contraídas com 5-HT pode atuar pela via do óxido nítrico (NO) ou pela da
cicloxigenase (COX). Quando são contraídas com histamina a via do NO não está
envolvida, no caso de HUA contraídas com KCl poderá existir um envolvimento da
endotelina-1. Em suma, estes dados foram ainda corroborados por modulação
computacional, onde se observou que o OMC tem afinidade para qualquer uma das
proteínas em estudo (eNOS, COX2, ETB e TXA2), apesar de ter uma afinidade superior
para a COX2. Em suma, o efeito vascular do OMC envolve a ativação de diferentes vias,
isto é, pode atuar pela via do NO, pela via da COX ou ainda ativar a via de endotelina-1.
Cardiovascular diseases (CVD) represent the number one cause of death worldwide. The vascular endothelium may play a role in the pathophysiology of CVD diseases. Octylmethoxycinnamate (OMC) is a UV-B filter widely used worldwide in numerous personal care products, including sunscreens, daily creams and makeup. Currently, OMC is considered an endocrine disruptor. Thus, the aim of this investigation was to evaluate the direct effects of Octylmethoxycinnamate (OMC) in human umbilical arteries with endothelium, and the possible mechanisms involved in the response. To this end, specific objectives were defined: 1. Isolation and culture of endothelial cells from human umbilical artery (HUA) and human umbilical vein (HUV); 2. Analysis of the direct effect of OMC in HUA with and without endothelium; 3. Analysis of the possible mechanisms involved in the effect of the COM in HUA with endothelium, mainly the effect on the signaling pathways of Nitric Oxide (NO) and Cyclooxygenases (COXs) 4. Computational analysis of the interaction of the COM with proteins involved in the endothelial signaling pathways. The results demonstrated that OMC exerts a rapid (non-genomic) and endotheliumdependent arterial relaxant effect when HUAs are previously contracted with serotonin (5- HT) and histamine (Hist). Relaxation in these arteries was more pronounced in the presence of endothelium, than in its absence, and in HUA contracted with Hist. On the other hand, when HUA were contracted with potassium chloride (KCl) this relaxing effect was only observed in HUA without endothelium, and it appeared to be inhibited in HUA with intact endothelium. Thus, the vasorelaxant effect of OMC not only depends on the endothelium, but was shown to be dependent on the contractile agent used, suggesting that OMC may act through different signaling pathways. Thus, when HUA are contracted with 5-HT it may act through the nitric oxide (NO) pathway or the cyclooxygenase (COX) pathway. When they are contracted with histamine the NO pathway is not involved, in the case of HUA contracted with KCl there may be an involvement of endothelin-1. In summary, these data were further corroborated by computational modulation, where it was observed that OMC has affinity for any of the proteins under study (eNOS, COX2, ET1 and TXA2), although it has a higher affinity for COX2. In summary, the vascular effect of OMC involves the activation of different pathways, i.e., it can act through the NO pathway, the COX pathway, or activate the endothelin-1 pathway.
Cardiovascular diseases (CVD) represent the number one cause of death worldwide. The vascular endothelium may play a role in the pathophysiology of CVD diseases. Octylmethoxycinnamate (OMC) is a UV-B filter widely used worldwide in numerous personal care products, including sunscreens, daily creams and makeup. Currently, OMC is considered an endocrine disruptor. Thus, the aim of this investigation was to evaluate the direct effects of Octylmethoxycinnamate (OMC) in human umbilical arteries with endothelium, and the possible mechanisms involved in the response. To this end, specific objectives were defined: 1. Isolation and culture of endothelial cells from human umbilical artery (HUA) and human umbilical vein (HUV); 2. Analysis of the direct effect of OMC in HUA with and without endothelium; 3. Analysis of the possible mechanisms involved in the effect of the COM in HUA with endothelium, mainly the effect on the signaling pathways of Nitric Oxide (NO) and Cyclooxygenases (COXs) 4. Computational analysis of the interaction of the COM with proteins involved in the endothelial signaling pathways. The results demonstrated that OMC exerts a rapid (non-genomic) and endotheliumdependent arterial relaxant effect when HUAs are previously contracted with serotonin (5- HT) and histamine (Hist). Relaxation in these arteries was more pronounced in the presence of endothelium, than in its absence, and in HUA contracted with Hist. On the other hand, when HUA were contracted with potassium chloride (KCl) this relaxing effect was only observed in HUA without endothelium, and it appeared to be inhibited in HUA with intact endothelium. Thus, the vasorelaxant effect of OMC not only depends on the endothelium, but was shown to be dependent on the contractile agent used, suggesting that OMC may act through different signaling pathways. Thus, when HUA are contracted with 5-HT it may act through the nitric oxide (NO) pathway or the cyclooxygenase (COX) pathway. When they are contracted with histamine the NO pathway is not involved, in the case of HUA contracted with KCl there may be an involvement of endothelin-1. In summary, these data were further corroborated by computational modulation, where it was observed that OMC has affinity for any of the proteins under study (eNOS, COX2, ET1 and TXA2), although it has a higher affinity for COX2. In summary, the vascular effect of OMC involves the activation of different pathways, i.e., it can act through the NO pathway, the COX pathway, or activate the endothelin-1 pathway.
Description
Keywords
Artéria Umbilical Humana Células Endoteliais Disruptor Endócrino Octilmetoxicinamato