Immunosuppression Drugs Exhibit Differential Effects on Endothelial Cell Function.

INTRODUCTION: Immunosuppressive medications are widely used to treat patients with neoplasms, autoimmune conditions, and solid organ transplants. Prior studies indicate that immunosuppression drugs can cause adverse vascular remodeling. Given the systemic effects of the drugs, elucidating cell-type-specific drug effects has been challenging. METHODS: We utilized induced pluripotent stem cell-derived endothelial cells to investigate the role of widely used immunosuppression drugs on endothelial cell function. RESULTS: We found that among immunosuppression agents, sirolimus reduced basic endothelial cell functions including cell migration, proliferation, acetylated LDL uptake, mitochondrial respiration, and angiogenic properties, while tacrolimus only reduced nitric oxide release. CONCLUSIONS: This model allows for investigation of differential effect of immunosuppression drugs on endothelial function that can elucidate the mechanisms contributing to clinically observed adverse vascular profiles.