In vitro modelling of the conditions found in endothelial erosion. (A) Photomicrographs of HCAECs, cultured under elevated flow for 72 h (7.5 Pa), with the experimental design of the in vitro model illustrated above. (B) Quantification of detachment in HCAECS cultured under elevated flow with the addition of TNFα (T-5 ng/mL) and CSE (C-10%) or both (TC), with the combined treatment resulting in a significant loss of cell adhesion (*P < 0.05, n = 6 donors). (C) Heatmap with identified clusters of gene expression changes identified in the transcriptomic analysis of the combined effects of oscillatory (OSS), laminar (LSS), and elevated (ESS) shear stress on HCAECs treated with control, 3 doses of 5 ng/mL TNFα (T), 3 doses of 10% CSE (C), or the combination of TNFα and CSE (TC), n = 3 donors. (D) Regulation of Ingenuity-defined Nrf2-mediated oxidative stress pathway compared with ESS control. (E) Top predicted canonical pathways by Ingenuity analysis, red indicates a predicted activation and green a decrease, with white suggesting dysregulation.