Correlações entre H₂S, NO e os biomarcadores plasmáticos na pré-eclâmpsia
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Data
2019-11-29
Autores
Pinto-Souza, Caroline Cristina
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Universidade Estadual Paulista (Unesp)
Resumo
A pré-eclâmpsia (PE) é uma síndrome hipertensiva (pressão arterial acima de 140/90 mmHg após 20 semanas de gravidez) que afeta de 4 a 7% de todas as gestações. As genitoras e fetos que apresentam essa anormalidade têm maior propensão a desenvolver doenças crônicas futuramente. Durante a PE ocorre uma redução nos níveis de óxido nítrico (NO), uma substância vasodilatadora derivada do endotélio, e essa queda é sinalizada na disfunção endotelial. Recentes pesquisas demonstraram a participação do sulfeto de hidrogênio (H₂S), uma molécula gasosa, nas funções cardiovasculares. Este gás compartilha diversas estruturas e funções com o NO, respondendo a vários estímulos, a citar, a regulação da contratilidade vascular e de sua integridade estrutural, além de ser pró-angiogênico. De modo significativo, estudos exprimiram que o decréscimo dos níveis plasmáticos do H₂S ou de suas enzimas produtoras ocorre na PE, ao mesmo tempo em que manifestaram como esse gás promoveu a fosforilação da eNOS em células endoteliais com consequente aumento da síntese de NO. Evidenciando, desse modo, o crosstalk entre esses dois gasotransmissores. Assim, a temática e o objetivo deste trabalho são a investigação dos níveis plasmáticos do H₂S e do NO, além de analisar possíveis correlações entre eles e os marcadores de estresse oxidativo: carbonil e malonaldeído (MDA); o nitrito plasmático, um metabólito estável do NO e o sFlt-1, um fator antiangiogênico. À vista disso, exploramos parâmetros clínicos e os marcadores em 120 mulheres com gestação saudável (GS), 88 com hipertensão gestacional (HAG) – síndrome hipertensiva com ausência da proteinúria e da lesão renal, e 62 com PE. A dosagem do H₂S plasmático e dos marcadores carbonil e MDA foi feita por métodos colorimétricos, a do nitrito plasmático, pela análise de quimioluminescência e a concentração do sFlt-1 no plasma foi determinada pelo ensaio imunoenzimático (ELISA). Constatamos diferenças significativas nas comparações entre a GS e a HAG e entre a GS e a PE nas variáveis clínicas IMC, pressão diastólica e sistólica (já esperadas nestas duas últimas), demonstrando como essas desordens hipertensivas na gestação possuem tais parâmetros alterados. No peso do recém-nascido; nas semanas gestacionais na coleta e no parto, houve contrastes relevantes entre a GS e a PE e entre a HAG e a PE. Com exceção do MDA, todos os marcadores apresentaram algum tipo de discrepância sugestiva entre os grupos. Quanto aos níveis de H₂S no plasma, observamos uma diferença significativa somente entre a GS e HAG (p < 0,01). Isto, mesmo que as médias se assemelham entre os grupos: GS (18,48); HAG (23,44) e PE (20,00). Considerando todas as categorias de medicamentos anti-hipertensivos, a média das concentrações plasmáticas de H₂S na HAG variaram entre 2,98μM e 67,17μM e na PE, entre 1,03μM e 51,36μM. Apresentaram correlações significativas com o nitrito plasmático, a HAG (p = 0,01) e a PE (p = 0,02) e esta última também exibiu um p significativo (< 0,01) com a carbonil. Logo, pelo o que foi supraposto, indicamos que existem correlações entre o H₂S, NO e os biomarcadores plasmáticos nos diferentes grupos experimentais apresentados.
Preeclampsia (PE) is a hypertensive syndrome (blood pressure above 140/90 mmHg after 20 weeks of pregnancy) that affects 4 to 7% of all pregnancies. Mothers and fetuses with this abnormality are more likely to develop chronic diseases in the future. During PE there is a reduction in the levels of nitric oxide (NO), an endothelium-derived vasodilator, and this drop is signaled in endothelial dysfunction. Recent researches have shown the role of hydrogen sulfide (H₂S), a gaseous molecule, in cardiovascular functions. This gas shares various structures and functions with NO, responding to various stimuli, to cite, the regulation of vascular contractility and its structural integrity, in addition to being pro-angiogenic. Significantly, studies have shown that the decrease in plasma levels of H₂S or its producing enzymes occurs in PE, while showing how this gas promoted eNOS phosphorylation in endothelial cells with consequent increase in NO synthesis. Thus evidencing the crosstalk between these two gas-transmitters. Thereby, the theme and objective of this work are the investigation of plasma levels of H₂S and NO, besides analyzing possible correlations between them and the markers of oxidative stress: carbonyl and malonaldehyde (MDA); plasma nitrite, a stable NO metabolite, and sFlt-1, an antiangiogenic factor. In view of this, we explored clinical parameters and markers in 120 women with healthy pregnancy (GS), 88 with gestational hypertension (HAG) - hypertensive syndrome without proteinuria and renal injury, and 62 with PE. Plasma H₂S, carbonyl and MDA markers were measured by colorimetric methods; the plasma nitrite by chemiluminescence analysis and plasma sFlt-1 concentration was determined by enzyme-linked immunosorbent assay (ELISA).We found significant differences in comparisons between GS and HAG and between GS and PE in the clinical variables BMI, diastolic and systolic pressure (already expected in the latter two), demonstrating how these hypertensive disorders in pregnancy have such altered parameters. In the weight of the newborn; in the gestational weeks at collection and delivery, there were relevant contrasts between GS and PE and between HAG and PE. With the exception of MDA, all markers showed some suggestive discrepancy between the groups. Regarding plasma H₂S levels, we observed a significant difference only between GS and HAG (p < 0.01). This, even though the averages are similar between the groups: GS (18.48); HAG (23.44) and PE (20.00). Considering all categories of antihypertensive drugs, the mean plasma concentrations of H₂S in HAG varied between 2.98μM and 67.17μM and in PE, between 1.03μM and 51.36μM. They showed significant correlations with plasma nitrite to HAG (p = 0.01) and PE (p = 0.02) and the latter also exhibited a significant p (< 0.01) with carbonyl. Therefore, from the above, we indicate that there are correlations between H₂S, NO and plasma biomarkers in the different experimental groups presented.
Preeclampsia (PE) is a hypertensive syndrome (blood pressure above 140/90 mmHg after 20 weeks of pregnancy) that affects 4 to 7% of all pregnancies. Mothers and fetuses with this abnormality are more likely to develop chronic diseases in the future. During PE there is a reduction in the levels of nitric oxide (NO), an endothelium-derived vasodilator, and this drop is signaled in endothelial dysfunction. Recent researches have shown the role of hydrogen sulfide (H₂S), a gaseous molecule, in cardiovascular functions. This gas shares various structures and functions with NO, responding to various stimuli, to cite, the regulation of vascular contractility and its structural integrity, in addition to being pro-angiogenic. Significantly, studies have shown that the decrease in plasma levels of H₂S or its producing enzymes occurs in PE, while showing how this gas promoted eNOS phosphorylation in endothelial cells with consequent increase in NO synthesis. Thus evidencing the crosstalk between these two gas-transmitters. Thereby, the theme and objective of this work are the investigation of plasma levels of H₂S and NO, besides analyzing possible correlations between them and the markers of oxidative stress: carbonyl and malonaldehyde (MDA); plasma nitrite, a stable NO metabolite, and sFlt-1, an antiangiogenic factor. In view of this, we explored clinical parameters and markers in 120 women with healthy pregnancy (GS), 88 with gestational hypertension (HAG) - hypertensive syndrome without proteinuria and renal injury, and 62 with PE. Plasma H₂S, carbonyl and MDA markers were measured by colorimetric methods; the plasma nitrite by chemiluminescence analysis and plasma sFlt-1 concentration was determined by enzyme-linked immunosorbent assay (ELISA).We found significant differences in comparisons between GS and HAG and between GS and PE in the clinical variables BMI, diastolic and systolic pressure (already expected in the latter two), demonstrating how these hypertensive disorders in pregnancy have such altered parameters. In the weight of the newborn; in the gestational weeks at collection and delivery, there were relevant contrasts between GS and PE and between HAG and PE. With the exception of MDA, all markers showed some suggestive discrepancy between the groups. Regarding plasma H₂S levels, we observed a significant difference only between GS and HAG (p < 0.01). This, even though the averages are similar between the groups: GS (18.48); HAG (23.44) and PE (20.00). Considering all categories of antihypertensive drugs, the mean plasma concentrations of H₂S in HAG varied between 2.98μM and 67.17μM and in PE, between 1.03μM and 51.36μM. They showed significant correlations with plasma nitrite to HAG (p = 0.01) and PE (p = 0.02) and the latter also exhibited a significant p (< 0.01) with carbonyl. Therefore, from the above, we indicate that there are correlations between H₂S, NO and plasma biomarkers in the different experimental groups presented.
Descrição
Palavras-chave
Pré-eclâmpsia, Sulfeto de hidrogênio, Óxido nítrico, Estresse oxidativo, Preeclampsia, Hydrogen sulphide, Nitric oxide, Oxidative stress