Vascular Dysfunction Induced by Testosterone in a Cross-Sex Hormone Therapy Model: Role of CD4+ Cells.

Vascular Dysfunction Induced by Testosterone in a Cross-Sex Hormone Therapy Model: Role of CD4+ Cells.

• Autor
• Jeimison Santos
• Co-autores
• Paula Barros , José Teles , Eduardo Damasceno , Carlos Sorgi , Lúcia Faccioli , José Carlos Alves , Rita Tostes
• Resumo

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  Introduction: The use of testosterone in gender-affirming therapy increases cardiovascular risk in transgender man. In contrast to female hormones, Testosterone has deleterious effects in the cardiovascular system. Sex differences in immune cells, with male exhibiting more proinflammatory CD4+ cells and females exhibiting more anti-inflammatory cells, are reported. This study investigates whether testosterone induces vascular dysfunction via activation of CD4+ cells in a cross-sex hormone therapy mouse model. Methods and Results: Female mice (C57/BL6) were treated with testosterone cypionate (T, 48 mg/Kg/week) for 8 weeks. To investigate whether castration (another gender affirming approach) enhances testosterone effects, a group were bilaterally ovariectomized (OVX) (CEUA-FMRP: 079/2019). Testosterone treatment increased serum testosterone levels, body mass index and gastrocnemius weight and reduced perigonadal fat weight in Sham and OVX mice, mimicking clinical findings. Testosterone treatment impaired endothelium-dependent vasodilation [Area under concentration-effect curve (AUC): Sham-Vehicle (V): 297,6 ± 12,9, n=6; Sham-T: 221,7 ± 12,2, n=9; OVX-V: 229,7 ± 19,5, n=9; OVX-T: 168,1 ± 16,6, n=9, p<0,05].  Long-term testosterone treatment (24 weeks) produced similar effects (AUC: Sham V: 301,5 ± 9,1, n=8; Sham T: 212,3±17,6, n=8). Testosterone had no effects on endothelium-dependent vasorelaxation in female mice lacking lymphocytes [Rag-1 knockout (KO)] (Rag-1 KO-V: 313,8 ± 13,2, n=6; Rag-1 KO-T: 318,2 ±18,1 n=7), or in female IL-17Ra or IL-22 KO mice. Adoptive transfer of CD4+ cells to Rag-1 KO mice restored testosterone effects on acetylcholine-induced vasodilation (AUC Rag-1 KO+CD4+ T: 224,0 ±13,4, n=8; p< 0.05). There were no differences in vasoconstriction among the experimental groups. Conclusion: Our results suggest that vascular dysfunction induced by testosterone is mediated by proinflammatory CD4+ cells, highlighting a potential clinical target to reduce the cardiovascular effects of testosterone in transgender man.

   

• Palavras-chave
• gender-affirming therapy, testosterone, CD4+ cells
• Modalidade
• Vídeos
• Área Temática
• Sistema endócrino e doenças vasculares