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Role of NRF2 and HO-1 in preeclampsia: polymorphisms, circulating factors and in vitro assays

Abstract

Preeclampsia is the leading cause of mortality and morbidity among pregnant women in Brazil and several countries. Its pathophysiology is complex and involves several processes, including the oxidative stress (increase of free radicals and/or decrease of antioxidant defense). Although evidences, clinical supplementation with vitamins (C and E) was not promising in preeclampsia. Currently, therapeutically the activation of transcription factor, NRF2 (nuclear factor, erythroid 2-like 2), has been explored in several diseases. This factor promote cytoprotection by activates the transcription of several antioxidant and detoxification proteins. Hemeoxigenase-1 (HO-1) is the most studied, because has antiapoptotic, anti-inflammatory and cytoprotection activities. Until now, only two studies have been performed in preeclampsia, using placenta or cytotrophoblast. Therefore, the aims of current project are compare among healthy pregnant and preeclampsia pregnant (responsive or nonresponsive to antihypertensive therapy) the frequencies of polymorphisms located in gene which encodes NRF2 and HO-1, the plasma levels of HO-1 and the antioxidant activity of plasma. Besides we will perform several studies in vitro incubating plasma with endothelial cell cultures and verify: NRF2 and HO-1 gene and protein expressions, NRF2 translocation, we will validate the NRF2 effects using siRNA against NRF2, and we will evaluate the microRNAs expressions which regulate NRF2. Also, cell viability and apoptosis will be evaluated here. Finally, aiming to improve preeclampsia therapy, we will use resveratrol (present in high quantities in grapes), an inductor of NRF2, in these cultures, and again all cells parameters will be evaluated. We believe that the data obtained in this project will provide relevant information to the study and therapy of preeclampsia in the global context. (AU)

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Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VIANA-MATTIOLI, SARAH; CINEGAGLIA, NAIARA; BERTOZZI-MATHEUS, MARIANA; BUENO-PEREIRA, THAINA OMIA; CALDEIRA-DIAS, MAYARA; CAVALLI, RICARDO CARVALHO; SANDRIM, VALERIA CRISTINA. SIRT1-dependent effects of resveratrol and grape juice in an in vitro model of preeclampsia. BIOMEDICINE & PHARMACOTHERAPY, v. 131, NOV 2020. Web of Science Citations: 1.
CINEGAGLIA, NAIARA; ACOSTA-NAVARRO, JULIO; RAINHO, CLAUDIA; ANTONIAZZI, LUIZA; MATTIOLI, SARAH; PIMENTEL, CAROLINE; SANTOS, RAUL D.; SANDRIM, VALERIA. Association of Omnivorous and Vegetarian Diets With Antioxidant Defense Mechanisms in Men. JOURNAL OF THE AMERICAN HEART ASSOCIATION, v. 9, n. 12 JUN 16 2020. Web of Science Citations: 0.
VIANA-MATTIOLI, SARAH; NUNES, PRISCILA; CAVALLI, RICARDO; SANDRIM, VALERIA. Analysis of SIRT1 Expression in Plasma and in an In Vitro Model of Preeclampsia. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2020, APR 28 2020. Web of Science Citations: 0.
VALERIA CRISTINA SANDRIM; MARCELO RIZZATTI LUIZON; ELIANE PILAN; MAYARA CALDEIRA-DIAS; FERNANDA BORCHERS COELI-LACCHINI; GEORGIA KORS; IULY BERNDT; RICCARDO LACCHINI; RICARDO CARVALHO CAVALLI. Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia. Revista Brasileira de Ginecologia e Obstetrícia, v. 42, n. 8, p. 460-467, Ago. 2020.
CALDEIRA-DIAS, MAYARA; MONTENEGRO, MARCELO F.; BETTIOL, HELOISA; BARBIERI, MARCO ANTONIO; CARDOSO, VIVIANE C.; CAVALLI, RICARDO C.; SANDRIM, VALERIA C. Resveratrol improves endothelial cell markers impaired by plasma incubation from women who subsequently develop preeclampsia. HYPERTENSION RESEARCH, v. 42, n. 8, p. 1166-1174, AUG 2019. Web of Science Citations: 0.
SANDRIM, VALERIA; COELI-LACCHINI, FERNANDA BORCHERS; TANUS-SANTOS, JOSE EDUARDO; LACCHINI, RICCARDO; CAVALLI, RICARDO CARVALHO. Circulating HO-1 levels are not associated with plasma sFLT-1 and GT(n) HMOX1 polymorphism in preeclampsia. HYPERTENSION IN PREGNANCY, v. 38, n. 2, p. 73-77, APR 3 2019. Web of Science Citations: 0.
SANDRIM, VALERIA C.; LUIZON, MARCELO R.; MACHADO, JACKELINE S. R.; CAVALLI, RICARDO C. C > T (rs17035945) polymorphism of TIMP-4 protects against preeclampsia. JOURNAL OF OBSTETRICS AND GYNAECOLOGY, v. 39, n. 1, p. 135-137, JAN 2 2019. Web of Science Citations: 0.
SANDRIM, VALERIA CRISTINA; MACHADO, JACKELINE; BETTIOL, HELOISA; BARBIER, MARCO ANTONIO; CARDOS, VIVIANE CUNHA; PALEI, ANA CAROLINA; CAVALLI, RICARDO CARVALHO. Circulating Tissue Inhibitor of Metalloproteinase-4 levels are not a Predictor of Preeclampsia in the period between 20 and 25 Weeks of Gestation. Revista Brasileira de Ginecologia e Obstetrícia, v. 40, n. 12, p. 757-762, DEC 2018. Web of Science Citations: 0.
LUIZON, MARCELO R.; PEREIRA, DANIELA A.; SANDRIM, VALERIA C. Pharmacogenomics of Hypertension and Preeclampsia: Focus on Gene-Gene Interactions. FRONTIERS IN PHARMACOLOGY, v. 9, FEB 28 2018. Web of Science Citations: 3.
SANDRIM, VALERIA C.; CALDEIRA-DIAS, MAYARA; BETTIOL, HELOISA; BARBIERI, MARCO ANTONIO; CARDOSO, VIVIANE CUNHA; CAVALLI, RICARDO CARVALHO. Circulating Heme Oxygenase-1: Not a Predictor of Preeclampsia but Highly Expressed in Pregnant Women Who Subsequently Develop Severe Preeclampsia. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018. Web of Science Citations: 0.
SANDRIM, VALERIA C.; DINIZ, SOLANGE; ELEUTERIO, NIBIA MARIANA; GOMES, KARINA B.; DUSSE, LUCI MARIA S.; CAVALLI, RICARDO C. Higher levels of circulating TIMP-4 in preeclampsia is strongly associated with clinical parameters and microRNA. CLINICAL AND EXPERIMENTAL HYPERTENSION, v. 40, n. 7, p. 609-612, 2018. Web of Science Citations: 2.

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