Angiotensin Converting Enzyme 90 kDa isoform: Biomarker for diagnosis of preeclampsia?

Preeclampsia (PE), one of the leading gestational hypertensive diseases, is characterized by increased blood pressure (⩾140/90mmHg) and pathological proteinuria after 20weeks gestation. It is a complex, multifactorial syndrome with an unestablished etiology and cure. The search continues for a biomarker that could assist in the early prediction or diagnosis of PE, reducing the rate of maternal and fetal mortality. Based on the findings of Casarini et al. that suggest the 90kDa isoform of the Angiotensin Converting Enzyme (ACE) as a possible marker of hypertension, we hypothesized that this isoform may be present in pregnant women with PE, since they present a transient and spontaneous model of systemic arterial hypertension in pregnancy. We believe, therefore, that pregnant women with pure PE (PPE) express the ACE 90kDa isoform in urine, as well as having elevated isoform enzymatic activity, during pregnancy only. Postpartum, with the normalization of blood pressure, the protein isoform would no longer be expressed. Pregnant women with superimposed preeclampsia (SPE) would present the ACE 90kDa isoform both during and after the gestation period, and its enzymatic activity would remain high as they are chronically hypertensive. It is expected that normotensive pregnant women do not present this isoform in their urine as elevated blood pressure levels do not occur. Both normotensive and PPE affected pregnant women with a family history of hypertension, will possibly express the ACE 90kDa isoform before pregnancy and may become hypertensive, only after some years, through the influence of environmental factors and/or other diseases. If our hypothesis is confirmed, it will allow differentiation of PPE and SPE sooner than 12weeks postpartum, which is currently the estimated period for confirmation of the specific diagnosis. Furthermore, it could be an early biomarker for predicting the disease, enabling the physician to choose the best clinical management. In addition, it would minimize the use of other methods as the biological sample for obtaining the marker is urine, a practical and effective test with good reproducibility. Finally, test results would enable a greater understanding of the mechanisms involved in gestational hypertension.

Aumento dos níveis do receptor solúvel da Interleucina-6 em pacientes com pré-eclâmpsia em relação a gestantes normotensas / Increased levels of the soluble receptor of interleukin-6 in patients withpreeclampsia compared to normotensive pregnant women

Objetivos: Comparar níveis plasmáticos do receptor solúvel da interleucina-6 (IL-6sR) entre gestantes normotensas e com pré-eclâmpsia.Métodos: Realizou-se coleta de sangue materno no período pré-parto de 21 pacientes com pré-eclâmpsia e 39 controles normotensas. As amostras foram armazenadas a menos 80°C até a análise laboratorial. Os níveis séricos de IL-6sR foram mensurados através do teste imunoenzimático ELISA. Para comparar os grupos foi utilizado teste t de Student. Consideraram-se significantes os resultados com P menor do que 0,05.Resultados: Os dados de gestantes com pré-eclâmpsia e gestantes normotensas, respectivamente, foram: idade materna 22,3±4,8 vs 26,0±3,7 anos (P=0,06); idade gestacional 32,7±5,8 vs 40,1±0,8 semanas (P=0,01); pressão arterial sistólica 143,0±2,2 vs 118,8±3,1 mmHg (P=0,01); pressão arterial diastólica 112,5±4,0 vs 77,2±10,2 mmHg (P=0,01); ácido úrico 5,87±1,10 vs 4,57±0,12 mg/dL (P=0,02); creatinina 0,82±0,12 vs 0,73±0,09 mg/dL (P=0,01); peso do recém-nascido 2.130,7±839,3 vs 3.555,0±261,0 gramas (P=0.01) e peso da placenta 621,3±167,0 vs 796,3±154,2 gramas (P=0,05).A relação proteinúria/creatininúria no grupo das pacientes com pré-eclâmpsia foi de 2,40±1,31. O valor de IL-6sR(ng/dL) na pré-eclâmpsia foi 28,7±10,8 vs 16,5±6,4 na gestante normotensa (P=0,01).Conclusões: Estes resultados mostram o aumento dos níveis plasmáticos do IL-6sR em pacientes com pré-eclâmpsia, em relação a gestantes normotensas. Mais estudos se mostram necessários para o esclarecimento da fisiopatologia desta entidade, como a análise de outras citocinas ligadas a esse receptor, visto que elas podem ser a chave para a resposta inflamatória sistêmica que ocorre nestas pacientes e, portanto, para o seu tratamento...

Aims: To compare Interleukin-6 soluble receptor (IL-6sR) plasmatic levels between normotensive pregnant controls and preeclamptic women.Methods: Maternal blood samples were collected before delivery from 21 patients with preeclampsia and 39 normotensive pregnant controls. Samples were stored at -80°C until laboratory assay. IL-6sR was measured by ELISA enzyme immunoassay. To compare groups Student's t test was used. Results with P less than 0.05 were considered significant.Results: Data from preeclampsia and normotensive pregnant controls were respectively: maternal age 22.3±4.8 vs 26.0±3.7 years (P=0.06); gestational age 32.7±5.8 vs 40.1±0.8 weeks (P=0.01); systolic blood pressure 143.0±2.2 vs 118.8±3.1 mmHg (P=0.01); diastolic blood pressure 112.5±4.0 vs 77.2±10.2 mmHg (P=0.01); uric acid 5.87±1.10 vs4.57±0.12 mg/dL (P=0.02); creatinine 0.82±0.12 vs 0.73±0.09 mg/dL (P=0.01); birth weight 2130.7±839.3 vs 3555.0±261.0 g (P=0.01); placental weight 621.3±167.0 vs 796.3±154.2 g (P=0,05). Proteinuria over creatininuria ratio in the preeclampsia group was 2.40±1.31. The concentration of IL-6sR (ng/dL) was 28.7±10.8 in preeclampsia vs 16.5±6.4 in normotensive pregnant controls (P=0.01).Conclusions: These results show an increased plasma levels of IL-6sRin patients with preeclampsia compared to normotensive pregnant women. More studies are necessary to clarify the pathophysiology of this entity, including the analysis of other cytokines linked to this receptor, due to the fact that they can be the key for the systemic inflammatory response that occurs in these patients and therefore for their treatment....