Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia.

OBJECTIVE: We examined the interaction of polymorphisms in the genes heme oxygenase-1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy. METHODS: The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA. CONCLUSION: We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.

OBJETIVO: Examinamos a interação dos polimorfismos nos genes heme oxigenase-1 (HMOX1) eóxido nítrico sintase (NOS3) em pacientes com pré-eclâmpsia (PE)bem como as capacidades de resposta à metildopa e à terapia anti-hipertensiva. MéTODOS: Os polimorfismos nos genes HMOX1 (rs2071746, A/T) e NOS3 (rs1799983, G/T) foram genotipados usando TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, EUA), e os níveis da enzima heme oxigenase-1 (HO-1) foram medidos por enzyme-linked immunosorbent assay (ELISA). RESULTADOS: Foram encontradas interações entre os genótipos da HMOX-1 e NOS3 e responsividade à metildopa, e que pacientes genotipados como AT apresentam níveis mais baixos de proteína HO-1 em comparação com o genótipo AA. CONCLUSãO: Foram encontradas interações entre os genes HMOX-1 e NOS3 e responsividade à metildopa e que o polimorfismo localizado no gene HMOX1 afeta os níveis de enzima HO-1 na resposta à metildopa e à terapia anti-hipertensiva. Esses dados sugerem o impacto da combinação desses dois polimorfismos na resposta anti-hipertensiva na PE.

Plasma levels of increased miR-195-5p correlates with the sFLT-1 levels in preeclampsia.

Although the role of soluble fms-like tyrosine kinase 1 (sFLT-1) in preeclampsia is well-established, the mechanism related to its synthesis remains poorly understood. We evaluated the association among the circulating microRNAs (miRs) and sFLT-1 levels in preeclampsia pregnant women. For this purpose, we measured the plasma sFLT-1 levels in 24 preeclampsia women and selected from these, three subjects with the lowest and three with the highest levels of sFLT-1 in order to screen for potential miRs associated with plasmatic sFLT-1 concentrations using a polymerase chain reaction-array (PCR-array) methodology. From screening results, we found three statistically different expressed miRs with fold change (FC-high/low levels) ≥3.0: miR-195-5p (FC = 5.2 increase in group with high sFLT-1 levels), miR-16-5p (FC = 3.2; increase in group with high sFLT-1 levels), and miR-375 (FC = -3.0; decrease in group with high sFLT-1 levels) which were later validated in all samples (n = 24). To correlate these miRs and plasma sFLT-1 levels, we used two extremes of analysis. In one part, we compared 12 preeclampsia women with the lowest sFLT-1 levels (L-50% group) to 12 with the highest levels (50% H group); and in the second analysis, 6 preeclampsia women (L-25%) from the L group to 6 preeclampsia women from the H group (H-25%). Our results showed increased expression of miR-195-5p in the H group, considering both the analyses with 50%, FC = 2.1 and 25%, FC = 4.2. Regarding other miRs, lack of correlation was found in both analyses (50% and 25%). In conclusion, our data demonstrate an association of higher levels of sFLT-1 with increased expression of miR-195-5p in preeclampsia pregnant women.