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Evaluation of the action of pravastatin on eNOS coupling and nitric oxide production in an in vitro model of pre-eclampsia

Grant number: 21/02570-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2021
Effective date (End): December 31, 2021
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal researcher:Valeria Cristina Sandrim
Grantee:Luísa Machado Pinheiro
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is a complex syndrome responsible for high maternal and perinatal morbidity and mortality in Brazil and worldwide. The causes and mechanisms by which this disease sets in have not been fully elucidated, however, it is believed that an abnormal implantation and placentation are responsible for generating a placental ischemia leading to a generalized endothelial dysfunction and release of placental factors in the maternal circulation. The imbalance between oxidative and antioxidant forces is one of the factors that contributes to the development of this endothelial dysfunction, as a consequence of oxidative stress, decreased availability of nitric oxide and increased production of O2- by NADPH Oxidase. The enzyme Nitric Oxide Endothelial Synthase (eNOS) on the other hand is responsible for the production of NO, an important vasodilator. However, it is important to notice that when uncoupled, this enzyme changes its production to O2-, capable of sequestering the remaining NO, further reducing its availability. In this circumstance, many studies have shown pravastatin as a potential drug for the treatment of pre-eclampsia, since through its pleiotropic effects this drug is likely to increase eNOS coupling and NO production, in addition to decreasing NADPH oxidase activity, being effective in improving endothelial dysfunction with the promotion of vasodilatory effects. In addition, the use of pravastatin as the statin of choice is justified by its low lipophilicity and limited transfer between mother and fetus, thus presenting a favorable safety profile. In order to observe the effects of pravastatin on pre-eclampsia, human umbilical cord vein endothelial cells (HUVECs) will be incubated with plasma from pre-eclamptic, hypertensive and healthy pregnant women, in the presence or absence of pravastatin.

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