The use of a human-derived placental unit model to study the role of the kinin-kallikrein system on placental Endothelial-Trophoblast interactions and angiogenesis

• Grant number: 19/09745-5
• Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): April 06, 2020
• Effective date (End): April 05, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Dulce Elena Casarini
• Grantee: Nayara Azinheira Nobrega Cruz
• Supervisor abroad: Mariane Bertagnolli
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Local de pesquisa : Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-del’Île-de-Montréal (CIUSSS-NIM), Canada
• Associated to the scholarship: 18/16653-7 - Analysis of alterations in renin-angiotensin and kallikreins-kinins systems in Pediatric Obesity and its contribution to associated complications, BP.DD

Abstract

This project tackles angiogenesis mechanisms responsible for new vessels formation in placenta during pregnancy, which are disrupted in complications including hypertensive disorders, diabetes and obesity, as well as in fetal programming of diseases. Even though impaired angiogenesis has been shown in severe hypertensive pregnancies, till now, the understanding of the mechanisms changing angiogenesis is very limited, particularly in the first trimester origin of placental dysfunction. This is relevant because one in ten pregnancies have hypertension. Hypertension disorders are responsible for 25% of all preterm births and fetal growth restriction, accounting for 76,000 maternal and 500,000 infant deaths each year. Further, consequences in surviving mothers and infants are beyond pregnancy, dramatically increasing their risks of cardiovascular and metabolic diseases across lifespan. These numbers reflect the insufficient knowledge on pathophysiological mechanisms causing hypertension in pregnancies and the consequent limited therapies to handle maternal circulatory changes, which could, collectively, enhance early interventions in high-risk pregnancies and prevent maternal and child diseases. The aim of this project is to underlie the role of a new mechanism recently described in placentas, the Kinin-Kallikrein System, and therapies modulating it on placental angiogenesis. To reach this goal, Dr. Bertagnolli's team have designed a human-derived placental unit model combining primary cultured of endothelial and trophoblast cells collected from placentas donated at the hospital Sacré-Coeur in Montréal. This innovative approach was built based on the unique expertise of CIUSSS -NIM research team aiming at accelerating the translation of obtained experimental knowledge to clinical investigations in this field.