RESUMEN
BACKGROUND: Transgender and nonbinary individuals face substantial cardiovascular health uncertainties. The use of gender-affirming hormone therapy can be used to achieve one's gender-affirming goals. As self-rated health is an important predictor of health outcomes, an understanding of how this association is perceived by transgender and nonbinary individuals using gender-affirming hormone therapy is required. The objective of this research was to explore transgender and nonbinary individuals' perceptions of cardiovascular health in the context of using gender-affirming hormone therapy. METHODS: In this qualitative study, English-speaking transgender and nonbinary adults using gender-affirming hormone therapy for 3 months or more were recruited from across Canada using purposive and snowball sampling methods. Semistructured interviews were conducted through videoconference to explore transgender and nonbinary individuals' perceptions of the association between gender-affirming hormone therapy and cardiovascular health between May and August 2023. Data were transcribed verbatim, and transcripts were analyzed independently by 3 reviewers using thematic analysis. RESULTS: Twenty-one participants were interviewed (8 transgender women, 9 transgender men, and 3 nonbinary individuals; median [range] age, 27 [20-69] years; 80% White participants). Three main themes were identified: cardiovascular health was not a primary concern in the decision-making process with regard to gender-affirming hormone therapy, the improved well-being associated with gender-affirming hormone therapy was felt to contribute to improved cardiovascular health, and health care provider knowledge and attitude facilitate the transition process. CONCLUSIONS: Gender-affirming hormone therapy in transgender and nonbinary individuals is perceived to improve cardiovascular health. Given the positive associations between care aligned with patient priorities, self-rated health, and health outcomes, these findings should be considered as part of shared decision-making and person-centered care.
RESUMEN
Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces the inflammatory stages of experimental atherogenesis, is released by macrophage (MΦ) exosomes and lowers cholesterol levels in atherosclerotic plaques. Recently, we discovered that natural autoantibodies directed against HSP27 enhance its signaling effects, as HSP27 immune complexes (IC) interact at the cell membrane to modulate signaling. We now seek to evaluate the potential role of the HSP27 IC on MΦ exosomal release and cholesterol export. First, in human blood samples, we show that healthy control subjects have 86% more exosomes compared to patients with coronary artery disease (p < 0.0001). Treating human THP-1 MΦ with rHSP27 plus a validated anti-HPS27 IgG antibody increased the abundance of exosomes in the culture media (+98%; p < 0.0001) as well as expression of Flotillin-2, a marker reflective of exosomal release. Exosome cholesterol efflux was independent of Apo-A1. THP-1 MΦ loaded with NBD-labeled cholesterol and treated with the HSP27 IC showed a 22% increase in extracellular vesicles labeled with NBD and a 95% increase in mean fluorescent intensity. In conclusion, exosomal abundance and secretion of cholesterol content increases in response to HSP27 IC treatment, which may represent an important therapeutic option for diseases characterized by cholesterol accumulation.