Placental vascularization disorders associated with renin angiotensin changes in pregnant women with COVID-19

• Grant number: 22/02452-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2022
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Dulce Elena Casarini
• Grantee: Nayara Azinheira Nobrega Cruz
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 17/17027-0 - Hormonal systems in renal and cardiovascular diseases: from cell biology to new physiological paradigms with advances for therapeutics, AP.TEM

Abstract

The impact of SARS-CoV-2 coronavirus infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme 2 (ACE2), which acts as the main receptor of SARS-CoV-2 in several cells and tissues, and especially in the placenta and utero-placental vessels, suggests vulnerability of this organ to viral infection during pregnancy. Beyond the risk of vertical transmission, which depends on additional molecular processes essential to allow the entry of the virus into this tissue, as well as its replication and manifestation of the disease. There is also the hypothesis that during SARS-CoV-2 entry into the cells ACE2 is dragged along with it leading to depletion of the membrane associated ACE2 and of its physiological functions on the tissue. During pregnancy, ACE2 has an important role in placentation, establishment of uteroplacental vascularization and in the cardiocirculatory adaptations to the hemodynamic changes imposed during pregnancy. Hypothesis: We postulate that such effects caused by SARS-CoV-2 on ACE2 may impair placentation and compromise maternal-fetal circulation, contributing to adverse clinical conditions and outcomes like those of other disorders of pregnancy such as pre-eclampsia and intrauterine growth restriction. Objectives: The main objective of this study is to evaluate renin angiotensin system (RAS) profile, specially ACE2 in placentas and umbilical cords from pregnancies with COVID-19 and with different severity, and to verify possible changes can be associated to vascular and structural alterations in the placenta, antiangiogenic and inflammatory profiles and to the maternal-fetal circulatory stress markers. Methods: Determine the expression of ACE2 and other RAS components in histologic sections of placenta and umbilical cord. Evaluate the polymorphism of ACE2 and ACE in these tissues. Perform the histopathological analysis of placentas and umbilical cords to evaluate malperfusion. Measure the level of cardiocirculatory stress markers present on tissue and umbilical cord blood. Perspective: Contribute to elucidate the role of ACE2 in pregnancy and potential implications in physiopathology of COVID-19 during pregnancy, this study aims to guide better maternal and child diagnosis and perinatal care to ultimately prevent chronic disease in this population.