Palmitate impairs angiogenesis via suppression of cathepsin activity

Angiogenesis requires the interaction of multiple variable factors to promote endothelial cell adhesion, migration and survival. Palmitate, a free fatty acid, exhibits an anti-angiogenic effect via interference with endothelial cell function, whereas cysteine proteases are important in protein turnover and are termed positive modulators of neovascularization. However, the association between these two factors regarding the regulation of human endothelial cell function remains to be elucidated. By using cell counting kit-8, the Transwell method and an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit, the present study reported that high levels of palmitate result in a significant decrease in endothelial cell proliferation and invasion, and induced cell apoptosis; cathepsin L and S inhibitors may suppress palmitate-induced apoptosis. Conversely, the results of the cathepsin L and S activity assay and reverse-transcription-quantitative polymerase chain reaction indicated that palmitate inhibited cathepsin-induced endothelial cell invasion, partially via suppressing the expression and activity of cathepsin L and S. The findings of the present study suggested that the potent anti-angiogenic properties of palmitate may be mediated by cysteine proteases.