Mechanical strain induces ceramide generation in endothelial cells

Ceramide and its metabolites have been implicated in numerous signaling pathways and can trigger cell type/stimulus-specific proliferation, differentiation, growth arrest, or apoptosis. We report that modulation of ceramide and its metabolites also occurs during the response of bovine aortic endothelial cells (bAECs) to mechanical strain, suggesting that ceramide signaling may affect the maintenance of a viable vascular endothelium during disease, vein grafting, and tissue engineering applications. Briefly, bAECs were exposed to 3%, 6%, 10%, or 12% cyclic strain at 1 Hz for up to 72 hrs and ceramide levels were investigated by mass spectrometry (MS). Additionally, ceramide levels were examined following cessation of 10% cyclic strain at 1 Hz for 24 hrs. MS analysis demonstrates that ceramide levels are elevated in response to cyclic mechanical strain, especially at or above 10% strain intensity. Our results suggest that ceramide regulation is fine-tuned to 6% strain. Following cessation of strain, ceramide levels quickly return to those of unstrained controls, suggesting that strain-related ceramide increases require continued application of strain. Using this knowledge of how ceramide is involved and regulated in response to mechanical stimulation, it may be possible to develop therapies to protect or enhance endothelial cells in tissue engineering and cell therapy applications. NIH 5 RO1 CA092389.