Comparação de padrões de dieta vegetariana versus onívora sobre o efeito de ativação da via NRF2 em células endoteliais
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Data
2019-07-24
Autores
Cinegaglia, Naiara da Costa
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Universidade Estadual Paulista (Unesp)
Resumo
Evidências apontam que a dieta vegetariana diminui a probabilidade de desenvolver doenças cardiovasculares (DCVs). Um dos principais mecanismos que levam às doenças cardiovasculares é a disfunção do endotélio, associada com a diminuição da biodisponibilidade de óxido nítrico (NO) e a produção excessiva de espécies reativas de oxigênio (ROS). Do ponto de vista de biomarcadores de estresse oxidativo/antioxidante e de envelhecimento biológico, enzimas com propriedades antioxidantes e o comprimento do telômero podem apresentar efeitos na modulação do sistema vascular. O presente estudo inclui dois manuscritos, sendo o primeiro relacionado a via de regulação NRF2/HO-1 e o segundo ao comprimento dos telômero em onívoros (ONI) e vegetarianos (VEG). No primeiro manuscrito, o objetivo foi verificar a concentração de HO-1 circulante, bem como investigar o efeito da incubação do plasma de ONI e VEG em células endoteliais sob a modulação da via NRF2/HO-1 e a produção de NO. Dos 745 indivíduos inicialmente recrutados, 44 ONI e 44 VEG do sexo masculino aparentemente saudáveis foram incluídos no estudo. A concentração de HO-1 circulante foi mensurado usando o ensaio de ELISA. As células endoteliais foram incubadas com amostras de plasma de ONI e VEG. Nós observamos que a concentração de HO-1 circulante foi maior nos ONI em relação aos VEG. A incubação das células endoteliais com o plasma de ONI induziu o aumento da expressão gênica/proteica do NRF2 e HO-1, bem como a atividade do ARE e a produção de NO, quando comparado com o grupo VEG. Estes achados indicam que a produção de HO-1 circulante nos ONI pode estar relacionada a um maior status pro-oxidativo. A ativação da via HO-1/NRF2 e a produção de NO em cultura de células endoteliais incubadas com o plasma de ONI, parece refletir um mecanismo adaptativo de proteção destas células contra possíveis danos. No segundo manuscrito, nosso objetivo foi avaliar o comprimento do telômero em leucócitos (LTL, do inglês leukocyte telomere length) nos ONI e VEG e sua associação com biomarcadores clássicos de risco cardiovascular. O LTL foi mensurado em 39 amostras de ONI e 41 de VEG através da reação em cadeia da polimerase (PCR) quantitativa em tempo real (RT-QPCR). Apesar de não haver diferença no comprimento do telômero entre ONI e VEG, uma forte correlação negativa entre LTL e a espessura intima-média da carótida (IMT, do inglês intima-media thickness) foi observada nos ONI, mas não no grupo VEG. Além disso, os ONI que foram classificados com o LTL curto apresentaram maior IMT comparado com VEG. Nossos achados sugerem que o comprimento do telomero pode ser utilizado como um marcador de aterosclerose subclinico no grupo de onívoros.
Several studies report that a vegetarian diet lowers the probability of developing cardiovascular diseases (CVDs). The endothelial dysfunction is one of the main mechanism that leads to CVDs, associated with decreased nitric oxide (NO) bioavailability and excessive production of reactive oxygen species (ROS). Regarding oxidative/antioxidant stress and biological aging biomarkers, enzymes with antioxidant properties and telomere length may have effects on vascular system modulation. The present study includes two manuscripts related to: 1) regulation of NRF2/HO-1 pathway and 2) telomere length in omnivorous (OMN) and vegetarians (VEG). In the first manuscript, our objectives were to verify circulating HO-1 levels and the effect of plasma incubation from omnivorous and vegetarians in endothelial cells on modulating of NRF2/HO-1 pathway and NO production. From 745 participants initially recruited, 44 omnivorous and 44 vegetarian men apparently healthy were included in this study and circulating HO-1 was measured using ELISA assay. Endothelial cells were incubated plasma samples from OMN and VEG. We found higher circulating HO-1 production in omnivorous compared to vegetarian. Moreover, the plasma collected from omnivorous was able to increase the gene/protein NRF2/HO-1 expression, ARE activity, and NO production in endothelial cells culture compared to vegetarian group. We suggest that HO-1 induction in omnivorous may indicate a pro-oxidative. Activation of the HO-1 / NRF2 pathway and NO production in endothelial cell culture incubated with ONI plasma seems to reflect an adaptive mechanism of protection of these cells against possible damage. In the second manuscript, our objectives were to evaluate leukocyte telomere length (LTL) in VEG and OMN subjects and its association with classical cardiovascular risk biomarkers. LTL was measured in 39 omnivorous and 41 vegetarians by Real-Time Quantitative PCR reaction. Although telomere length was not different between omnivorous and vegetarians, we found a strong negative correlation between LTL and intima-media thickness (IMT) in omnivorous, but not in vegetarian group. In addition, omnivorous who were classified with short telomere length had higher carotid IMT compared to vegetarians. Our data suggest that telomere length can be a marker of subclinical atherosclerosis in the omnivorous group.
Several studies report that a vegetarian diet lowers the probability of developing cardiovascular diseases (CVDs). The endothelial dysfunction is one of the main mechanism that leads to CVDs, associated with decreased nitric oxide (NO) bioavailability and excessive production of reactive oxygen species (ROS). Regarding oxidative/antioxidant stress and biological aging biomarkers, enzymes with antioxidant properties and telomere length may have effects on vascular system modulation. The present study includes two manuscripts related to: 1) regulation of NRF2/HO-1 pathway and 2) telomere length in omnivorous (OMN) and vegetarians (VEG). In the first manuscript, our objectives were to verify circulating HO-1 levels and the effect of plasma incubation from omnivorous and vegetarians in endothelial cells on modulating of NRF2/HO-1 pathway and NO production. From 745 participants initially recruited, 44 omnivorous and 44 vegetarian men apparently healthy were included in this study and circulating HO-1 was measured using ELISA assay. Endothelial cells were incubated plasma samples from OMN and VEG. We found higher circulating HO-1 production in omnivorous compared to vegetarian. Moreover, the plasma collected from omnivorous was able to increase the gene/protein NRF2/HO-1 expression, ARE activity, and NO production in endothelial cells culture compared to vegetarian group. We suggest that HO-1 induction in omnivorous may indicate a pro-oxidative. Activation of the HO-1 / NRF2 pathway and NO production in endothelial cell culture incubated with ONI plasma seems to reflect an adaptive mechanism of protection of these cells against possible damage. In the second manuscript, our objectives were to evaluate leukocyte telomere length (LTL) in VEG and OMN subjects and its association with classical cardiovascular risk biomarkers. LTL was measured in 39 omnivorous and 41 vegetarians by Real-Time Quantitative PCR reaction. Although telomere length was not different between omnivorous and vegetarians, we found a strong negative correlation between LTL and intima-media thickness (IMT) in omnivorous, but not in vegetarian group. In addition, omnivorous who were classified with short telomere length had higher carotid IMT compared to vegetarians. Our data suggest that telomere length can be a marker of subclinical atherosclerosis in the omnivorous group.
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Palavras-chave
células endoteliais, dieta vegetariana, heme-oxigenase, risco cardiovascular, comprimento do telômero, endothelial cells, vegetarian diet, heme-oxygenase, cardiovascular risk, telomere length