ABSTRACT
Abstract Objective To evaluate whether the circulating level of tissue inhibitor of metalloproteinase- 4 (TIMP-4) in the period between 20 and 25 weeks of gestation is a predictor of preeclampsia. Methods We have performed a case-control study, nested in a prospective study cohort in Ribeirão Preto, in the state of São Paulo, Brazil. Of the 1,400 pregnant women evaluated between 20 and 25 weeks of gestation, 460 delivered in hospitals outside of our institution. Of the 940 pregnant women who completed the protocol, 30 developed preeclampsia. Healthy pregnant women (controls, n = 90) were randomly selected from the remaining 910 participants. From blood samples collected between 20 and 25 weeks of gestation, we performed a screening of 55 angiogenesis-related proteins in 4 cases and 4 controls. The protein TIMP-4 was the most differentially expressed between cases and controls. Therefore, wemeasured this protein in all cases (n = 30) and controls selected (n = 90). Results There were no differences in the plasma TIMP-4 levels of cases compared with controls (1,144 263 versus 1,160 362 pg/mL, respectively; p > 0.05). Conclusion Plasma TIMP-4 levels were not altered at 20 to 25 weeks of gestation, before the manifestation of clinical symptoms; therefore, they are not good predictors of the development of preeclampsia.
Resumo Objetivo Avaliar se o nível de inibidor tecidual de metaloproteinases tipo-4 (TIMP-4, na sigla em inglês) circulante no período entre 20 e 25 semanas de gestação é um preditor de preeclâmpsia. Métodos Foi realizado um estudo caso-controle aninhado em uma coorte de estudo prospectivo em Ribeirão Preto, São Paulo, Brasil. De 1.400 mulheres grávidas avaliadas entre 20 e 25 semanas de gestação, 460 tiveram parto em hospitais fora da nossa instituição. Das 940 gestantes que completaram o protocolo, 30 desenvolveram preeclâmpsia. Gestantes saudáveis (controles, n = 90) foram selecionadas aleatoriamente das 910 participantes restantes. A partir de amostras de sangue coletadas entre 20 e 25 semanas de gestação, foi realizada uma triagem de 55 proteínas relacionadas à angiogênese em 4 casos e 4 controles. A proteína TIMP-4 foi a mais diferentemente expressa entre os casos e os controles; portanto, medimos esta proteína em todos os casos (n = 30) e controles selecionados (n = 90). Resultados Não houve diferenças nos níveis plasmáticos de TIMP-4 nos casos em comparação com os controles (1.144 263 versus 1.160 362 pg/mL, respectivamente; p > 0,05). Conclusão Os níveis plasmáticos de TIMP-4 não foramalterados no período entre 20 e 25 semanas de gestação antes da manifestação dos sintomas clínicos; portanto, não são um bom preditor do desenvolvimento da preeclâmpsia.
Subject(s)
Humans , Female , Pregnancy , Adult , Pre-Eclampsia/blood , Pregnancy Trimester, Second/blood , Tissue Inhibitor of Metalloproteinases/blood , Case-Control Studies , Predictive Value of TestsABSTRACT
Aim To observe whether matrix metallo-proteinase-14 ( MMP-14) and tissue matrix metallopro-teinase inhibitor-4 ( TIMP-4) were involved in the car-diac-protection of mitochondrial aldehyde dehydrogen-ase 2 ( ALDH2) against high glucose induced rat pri-mary cardiomyocyte injury. Methods Rat primary cardiomyocytes were cultured. The cardiomyocyte via-bility was detected by MTT assay at different concentra-tion of glucose at different time point. After established high glucose-induced cardiomyocytes injury model, cardiomyocytes were randomly divided into 4 groups:normal control group ( NG, glucose at 5.5 mmol· L-1) , NG + Alda-1 group ( Alda-1 at 20 μmol·L-1) , high glucose group ( HG, glucose at 30 mmol·L-1) and HG+Alda-1 group. The cell viability at 48 h and oxidative stress level were detected by MTT and DHE staining methods. The protein expressions of ALDH2, MMP-14 and TIMP-4 were determined by Western blot. Results The cardiomyocytes injury model was established according to the cell activity result. Com-pared with NG group, the cell viability, the protein ex-pressions of ALDH2, MMP-14, the ratio of MMP-14/TIMP-4 were decreased, TIMP-4 protein expression and the level of oxidative stress were increased in HG group. Compared with HG group, in HG + Alda-1 group, the cell viability, the protein expressions of AL-DH2, MMP-14, the ratio of MMP-14/TIMP-4 were in-creased, the levels of oxidative stress and TIMP-4 pro-tein expression were decreased. Conclusion Activa-tion of mitochondrial ALDH2 may relieve high glucose induced cardiomyocytes injury. The protective effect was likely related to the inhibition of oxidative damage, down-regulation of MMP-14 and up-regulation of TIMP-4 proteins.