Tissue Derivation and Biological Sex Uniquely Mediate Endothelial Cell Protein Expression, Redox Status, and Nitric Oxide Synthesis

Human endothelial cells are routinely utilized in cardiovascular research to provide a translational foundation for understanding how the vascular endothelium functions in vivo. However, little attention has been given to whether there are sex specific responses in vitro. Similarly, it is unclear whether endothelial cells derived from distinct tissues behave in a homogenous manner. Herein, we demonstrate that marked sex differences exist within, and between, commonly utilized human primary endothelial cells from healthy donors, with respect to redox status, nitric oxide synthesis, and associated proteins that can mediate their expression. Further, we demonstrate that endothelial cells respond uniquely to inflammatory insult in a sex- and tissue origin-dependent manner. Our findings suggest sex and tissue derivation may need to be considered when studying endothelial cells in vitro as cells derived from distinct tissue and sexes may not behave interchangeably.