Effect of hyperuricemia in the plasma of pregnant women with preeclampsia on autophagy in mononuclear lymphoid cells

• Grant number: 14/00693-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: April 01, 2014
• End date: April 30, 2014
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Mariana Leticia Matias
• Supervisor: Steven S. Witkin
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Weill Cornell Medical College, United States
• Associated to the scholarship: 12/21287-3 - Analysis of inflammasome induced by urate monosodium in monocytes from pregnant women with preeclampsia, BP.MS

Abstract

Preeclampsia (PE) is a clinical complication of pregnancy characterized by hypertension and proteinuria, identified after the 20th week of gestation. This pathology is associated with hyperuricemia, elevated plasma levels of inflammatory cytokines, leukocyte activation and oxidative stress. High levels of uric acid in the plasma of pregnant women with PE have been considered not only as a marker of severity, but represent a direct contribution to the pathogenesis of PE. Uric acid crystals can activate an intracellular complex called inflammasome, a major multi - protein structure for processing and release of inflammatory cytokines IL-1 b and IL-18. On the other hand, the intracellular catabolic process called autophagy, which removes damaged organelles and cytoplasmic proteins appears to be a potent anti-inflammatory mechanism, which controls the activation of inflammasomes and is able to maintain cellular homeostasis. Considering that hyperuricemia is a common finding in pregnancies complicated with PE associated with severity, oxidative stress and elevated levels of inflammatory cytokines present in the plasma of patients, this study aims to assess whether plasma levels of uric acid in pregnant women with PE can inhibit autophagy in vitro by mononuclear lymphoid cells, and whether this effect can vary with the concentration of uric acid in the plasma. Forty pregnant women will be studied, being 20 normotensive and 20 women with PE, matched for gestational age, and 20 healthy non-pregnant women. Peripheral blood mononuclear cells (5 x 105) obtained from healthy non-pregnant women will be incubated at 37oC in a constant atmosphere of 5% CO2 in the presence or absence of 10 % plasma from normotensive pregnant women or preeclamptic women. As a control, the test will be performed in the presence or absence of rapamycin, autophagy inducing in a concentration of 800 mmol /L. Control cultures will be performed in the presence of 10 % fetal bovine serum and different concentrations of monosodium urate. After 48 h culture the cells will lysed and the p62 protein determined in the cell supernatant by enzyme immunoassay (ELISA). (AU)