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Testosterone-induced cardiac dysfunction in an experimental model of gender-affirmating hormone therapy

Grant number: 22/11467-6
Support Opportunities:Scholarships in Brazil - Program to Stimulate Scientific Vocations
Effective date (Start): January 11, 2023
Effective date (End): March 02, 2023
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Rita de Cassia Aleixo Tostes Passaglia
Grantee:Jean Carlos Soares da Silva
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Testosterone is used in the process of gender transition by transmale people and, although safe, it increases cardiovascular risk for this population. In pathophysiological contexts, testosterone exerts deleterious effects on the cardiovascular system, with pro-hypertrophic effects in the heart. Effector CD4+ T lymphocytes contribute to the cardiac remodeling process, an effect observed in different experimental models. Testosterone also interferes with the cellular metabolism, increasing the activity of the glycolytic pathway. Changes in energy metabolism, especially in glycolytic metabolism, favor the differentiation of CD4+ T lymphocytes to pro-inflammatory profiles. Considering that cells of the immune system, including CD4+ T lymphocytes, are involved in cardiac dysfunction and that testosterone increases glycolytic metabolism, the hypothesis of our study is that the treatment of female mice with testosterone - an experimental hormone model - induces cardiac morphofunctional dysfunction by increased glycolytic metabolism in CD4+ T lymphocytes. We will evaluate the participation of CD4+ T lymphocytes in the inflammatory process associated with testosterone-induced cardiac dysfunction. Cardiac morphofunctional parameters will be evaluated by echocardiography and histological techniques in female mice deficient in B and T lymphocytes [Rag1 knockout (KO)] that will receive CD4+ T lymphocytes after treatment with vehicle or testosterone (48 mg.Kg-1.week-1). In WT females, serum levels of pro-inflammatory cytokines will be measured, and the profile and location of CD4+ T lymphocytes in cardiac tissue will be evaluated by flow cytometry and confocal microscopy, respectively. (AU)

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