Document Type

Presentation

Publication Date

Fall 10-5-2026

Abstract

Doxorubicin (DOX) is an effective chemotherapeutic agent whose clinical use is limited by cardiovascular toxicity. In addition to direct cardiomyocyte injury, vascular endothelial dysfunction may contribute to chemotherapy-associated cardiovascular injury. Our broader research investigates whether DOX-induced monocyte changes influence endothelial cells through secreted factors and potentially extracellular-vesicle-associated signaling. Preliminary data demonstrated that DOX increases human endogenous retrovirus-K (HERV-K) mRNA expression in THP-1 monocytes. We sought to establish an in vitro monocyte–endothelial conditioned-medium transfer model and identify appropriate controls for evaluating monocyte-derived effects on endothelial cells. THP-1 monocytes and EA.hy926 endothelial cells were cultured under optimized conditions. As an initial model-development experiment, EA.hy926 cells were exposed to standard endothelial medium or THP-1-conditioned RPMI. Ongoing experiments compare standard endothelial medium, fresh THP-1/RPMI medium, and THP-1-conditioned RPMI to distinguish effects of medium composition from factors released by monocytes. Future studies will compare conditioned media from vehicle- and DOX-treated THP-1 monocytes and assess endothelial morphology and junctional organization by immunofluorescence. DOX increased HERV-K mRNA expression in THP-1 monocytes. EA.hy926 cells remained adherent in THP-1-conditioned RPMI but exhibited a more elongated, spindle-shaped morphology than cells cultured in endothelial medium. These observations establish the foundation for a controlled monocyte–endothelial transfer model and emphasize the need for medium-specific controls before attributing endothelial changes to monocyte-derived factors.

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