IDENTIFICATION OF NEW ENDOTHELIAL DYSFUNCTION PATHWAYS ASSOCIATED TO PREECLAMPSIA.

IDENTIFICATION OF NEW ENDOTHELIAL DYSFUNCTION PATHWAYS ASSOCIATED TO PREECLAMPSIA.

• Autor
• Sarah Viana Mattioli
• Co-autores
• Valéria Cristina Sandrim
• Resumo

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  Preeclampsia (PE), a hypertensive disorder of pregnancy responsible for a large part of the annual maternal-fetal morbidity and mortality values, has a complex pathophysiology that is not yet fully understood. It is known that release of factors by ischemic placenta in the maternal circulation contributes to systemic endothelial dysfunction. Therefore, the most used model to study maternal endothelial dysfunction involves the incubation of endothelial cells (ECs) with the plasma of PE women. However, this model is limited by the absence of hemodynamic forces, to which ECs are exposed in vivo. Shear stress (SS), the frictional force of the blood flow that acts on the surface of ECs, activates several mechanotransduction pathways capable of modifying intracellular signaling, gene expression and protein expression. Given that, it is possible that important pathways are not being evaluated in the static model studied so far. Furthermore, few studies evaluated the effects of PE plasma in ECs on global gene expression and no study has evaluated this model exposed to SS.

  Objective: identify and characterize altered pathways by the incubation of EC with PE plasma in an in vitro model subjected to SS and oscillatory SS (OSS) in comparison to gestational hypertension (GH) and healthy pregnant women (HP). Moreover, in a second step, we intend test drugs that act in these pathways reversing endothelial dysfunction in PE.

  Methods: Human Coronary Artery Endothelial Cells (HCAEC) cultivated in the IBIDI SS equipment (Ibidi, Martinsried, Germany) will be incubated with the pool of plasma (n=10) of 20 HP, GH and PE women. Then, total RNA will be analyzed using GeneTitan™ Microarray System. The Microarray results will guide the project’s future investigations and the choice of drugs that will be tested. Moreover, classical pathways involved in the endothelial dysfunction will also be evaluated, using Western Blot, immunohistochemistry, and intracellular probes.

   

• Palavras-chave
• Preeclampsia; Shear-stress; Plasma; Endothelial dysfunction
• Modalidade
• Pôster
• Área Temática
• Revisões, projetos, revisões sistemáticas e metanálises em biologia vascular