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Arginase in preeclampsia: study of genetic polymorphism, circulating factors and in vitro assays

Abstract

Preeclampsia is the main cause of mortality and morbidity among pregnant women in Brazil and in several countries. The pathophysiology of this disease is complex and involves several processes. One of them is related to deficiency of the nitric oxide (NO). A possible cause of this deficiency could be the high expression of the enzyme arginase, which competes for the substrate (L-arginine) with eNOS, an enzyme that produces NO mainly in the endothelium, thus reducing the available substrate for NO synthesis. To date, few studies have focused on the study of arginase in preeclampsia, none of which evaluates genetic polymorphisms that could modulate their enzymatic activity and consequently contribute to changes in NO bioavailability. Thus, the present project aims to compare the frequencies of polymorphisms in the genes coding for arginase 1 and arginase 2 between healthy pregnant women and preeclampsia (responsive or not to antihypertensive therapy), the plasma levels of these enzymes, their activity and the correlation of these variables with plasma levels of nitrite (NO biomarker) and sFLT-1. In addition, we will perform in vitro studies (in vitro model of pre-eclampsia) by incubating the plasma of these pregnant women with endothelial cells, together with the arginase inhibitor (BEC) and a potential NADPH oxidase inhibitor (resveratrol) and checking: arginase activity, cytotoxicity, cell viability, apoptosis, production of reactive oxygen species, NO, among other parameters. We believe that the data obtained in this project will bring information relevant to the study and therapy of preeclampsia in the world context. (AU)

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Scientific publications (4)
(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)
CRUZ, JULIANA DE O.; CONCEICAO, IZABELA M. C. A.; SANDRIM, VALERIA C.; LUIZON, MARCELO R. p Comprehensive analyses of DNA methylation of the TIMP3 promoter in placentas from early-onset and late-onset preeclampsia. Placenta, v. 117, p. 118-121, JAN 2022. Web of Science Citations: 0.
PINTO-SOUZA, CAROLINE C.; COELI-LACCHINI, FERNANDA; LUIZON, MARCELO R.; CAVALLI, RICARDO C.; LACCHINI, RICCARDO; SANDRIM, VALERIA C. Effects of arginase genetic polymorphisms on nitric oxide formation in healthy pregnancy and in preeclampsia. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 109, p. 20-25, MAY 1 2021. Web of Science Citations: 0.
AMARAL, LORENA M.; SANDRIM, VALERIA C.; KUTCHER, MATTHEW E.; SPRADLEY, FRANK T.; CAVALLI, RICARDO C.; TANUS-SANTOS, JOSE E.; PALEI, ANA C. Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 2 JAN 2021. Web of Science Citations: 0.
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.

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