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Analysis of arginase expression and enzymatic activity and its modulation by resveratrol in preeclampsia in vitro model

Grant number: 19/26640-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2020
Effective date (End): December 31, 2020
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Valeria Cristina Sandrim
Grantee:Thainá Omia Bueno Pereira
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

In Brazil and worldwide, preeclampsia (PE) stands out as one of the main causes of maternal mortality and perinatal morbity. The understanding of the PE pathophysiology is still limited, but it is know that there is placental hypoperfusion and release of placental factors in the maternal circulation that causes generalized endothelial dysfunction, leading to systemic vascular dysfunction. Arginase is the urea cycle regulatory enzyme existing in two isoforms, arginase I, expressed in smooth muscle cells, and arginase II, mostly expressed in the endothelium. Previous studies indicate that arginase II is excessively increased in the placenta of women with PE and this increase is directly related to the nitric oxide (NO) pathway. Arginase competes for the same substrate as the enzyme eNOS (L-arginine), causing its depletion and consequently eNOS uncoupling. Thus, it is of great interest to produce research for possible arginase inhibitors. Resveratrol is a potent natural antioxidant found in grape skins that is capable to increase NO concentrations in cells that have been incubated with plasma from preeclamptic women and decrease superoxide production in treated mice, thereby preventing eNOS uncoupling. To evaluate the relationship between arginase and Resveratrol, under the context of PE, in an in vitro model, human umbilical vein endothelial cells (HUVECs) will be incubated with plasma from healthy, hypertensive and preeclamptic pregnant woman in the presence or absence of Resveratrol. In addition, the expression and activity of arginase will be analyzed, as well the reactive species of oxygen and nitric oxide.