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


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)

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