Importance of female sex hormones and menopause in brain dead donors: identification of miRNAs as markers of organ quality

• Grant number: 23/00728-6
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Cristina Breithaupt Faloppa
• Grantee: Ana Cristina Breithaupt Faloppa
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Cristiano de Jesus Correia ; Fernanda Yamamoto Ricardo da Silva ; Hendrik Gerrit Derk Leuvenink ; Luiz Felipe Pinho Moreira

Abstract

Organ transplantation is a treatment option for patients in advanced stages of the disease, however the reduced number of available organs is an obstacle to its effectiveness. Current data show that there is a great difference between the number of patients who need an organ for transplantation and the number of possible donors. In Brazil, in 2021, the number of potential donors was 5,846, but only 20% became effective donors (RGT 2021, ABTO). The high demand of patients on the waiting list for organs for transplantation makes the criteria for the use of marginal donors more flexible and among these donors, with the aging of the population, there is an increase in the inclusion of older donors. Among effective donors in Brazil in 2021, 46% were over 50 years old (RGT 2021, ABTO).Brain dead patients are one of the main sources of organs for transplantation, mainly heart and lungs. Clinical and experimental studies confirm the donor's sex as one of the factors that influence the outcome of heart and lung transplantation. Considering the importance of female sex hormones in the development of systemic inflammation, studies have shown protective effects of estradiol treatment in the lungs and hearts of female rats after brain death (BD). The data show that treatment with estradiol attenuates pulmonary and cardiac inflammation, reducing the leukocyte infiltrate and decreasing the pulmonary release of inflammatory mediators and cardiomyocyte apoptosis. A more dysfunctional endothelium in the older graft may be a major causative factor because endothelial dysfunction, which is known to increase with age, leads to a more pro-inflammatory endothelium that favors atherosclerotic processes. In the context of cardiovascular alterations, the menopause period is characterized by the establishment of important alterations that contribute to the increase in morbidity and mortality of women after 50 years of age. miRNAs involved in immune regulation differ between sexes and are altered during aging, therefore understanding their role and identifying these molecules in the pathogenesis of BD in lungs and heart could provide biomarkers and enable studies of the use of previously unusable donor organs.Therefore, the objective of this project will be to investigate the effects of menopause/aging and treatment with the agonist of the membrane estradiol receptor (GPER) in rats submitted to brain death. At the same time, identify changes in the expression of miRNAs in lung and heart tissue, analyzing activated signaling pathways and histopathological changes resulting from brain death. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RICARDO-DA-SILVA, FERNANDA Y.; DE FREITAS, PEDRO LUIZ Z.; VIDAL-DOS-SANTOS, MARINA; MIOLA, ELIZABETH CRISTINA; ARMSTRONG-, ROBERTO, JR.; CORREIA, CRISTIANO J.; MOREIRA, LUIZ FELIPE P.; BREITHAUPT-FALOPPA, ANA CRISTINA. The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats. TRANSPLANTATION, v. 108, n. 9, p. 1-pg., 2024-09-01. (21/13020-6, 23/00728-6)

RICARDO-DA-SILVA, FERNANDA Y.; DE FREITAS, PEDRO LUIZ Z.; VIDAL-DOS-SANTOS, MARINA; MIOLA, ELIZABETH CRISTINA; ARMSTRONG-JR, ROBERTO; CORREIA, CRISTIANO J.; MOREIRA, LUIZ FELIPE P.; BREITHAUPT-FALOPPA, ANA CRISTINA. The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats.. TRANSPLANTATION, v. 108, n. 9S, p. 1-pg., 2024-09-01. (21/13020-6, 23/00728-6)

VITAGLIANO, TENNILLE L.; DE LA MATA, NICOLE L.; HSU, PETER S.; ALEXANDER, STEPHEN; WYBURN, KATE; WYLD, MELANIE. The impact of female sex and intersectional disadvantage on access to deceased kidney transplantation in australia: A 15 year national cohort study.. TRANSPLANTATION, v. 108, n. 9S, p. 1-pg., 2024-09-01. (23/00728-6)

MIOLA, ELIZABETH CRISTINA; RICARDO-DA-SILVA, FERNANDA YAMAMOTO; DE FREITAS, PEDRO LUIZ ZONTA; VIDAL-DOS-SANTOS, MARINA; MOREIRA, LUIZ FELIPE PINHO; BREITHAUPT-FALOPPA, ANA CRISTINA; CORREIA, CRISTIANO DE JESUS. The role of sex hormones in the intestinal injury after brain death using a surgical menopause model in rats. Molecular and Cellular Endocrinology, v. 600, p. 9-pg., 2025-02-20. (21/13020-6, 23/00728-6, 20/11211-6)

MIOLA, ELIZABETH C.; RICARDO-DA-SILVA, FERNANDA Y.; DE FREITAS, PEDRO L. Z.; VIDAL-DOS-SANTOS, MARINA; CORREIA, CRISTIANO J.; MOREIRA, LUIZ FELIPE P.; FALOPPA, ANA CRISTINA BREITHAUPT. A study of menopause effects on lung inflammation after brain death using a model of transitional follicular depletion with aging.. TRANSPLANTATION, v. 108, n. 9S, p. 1-pg., 2024-09-01. (23/00728-6)

MIOLA, ELIZABETH C.; RICARDO-DA-SILVA, FERNANDA Y.; DE FREITAS, PEDRO L. Z.; VIDAL-DOS-SANTOS, MARINA; CORREIA, CRISTIANO J.; MOREIRA, LUIZ FELIPE P.; BREITHAUPT FALOPPA, ANA CRISTINA. A study of menopause effects on lung inflammation after brain death using a model of transitional follicular depletion with agin. TRANSPLANTATION, v. 108, n. 9, p. 1-pg., 2024-09-01. (23/00728-6)