Proteomic profiling of endorepellin angiostatic activity on human endothelial cells

Background: Endorepellin, the C-terminal domain V of the heparan sulfate proteoglycan perlecan, exhibits powerful and targeted anti-angiogenic activity on endothelial cells. To identify proteins involved with endorepellin anti-angiogenic action, we performed an extensive comparative proteomic analysis between vehicle- and endorepellin-treated human endothelial cells. Results: Proteomic analysis of endorepellin influence on human umbilical vein endothelial cells identified five differentially expressed proteins, three of which (beta-actin, calreticulin, and chaperonin/ Hsp60) were down-regulated and two of which ( vimentin and the beta subunit of prolyl 4-hydroxylase also known as protein disulfide isomerase) were up-regulated in response to endorepellin treatment-and associated with a fold change (endorepellin/control) <= 0.75 and >= 2.00, and a statistically significant p-value as determined by Student's t test. Conclusion: The proteins identified represent potential target areas involved with endorepellin anti-angiogenic mechanism of action. Further elucidation as such will ultimately provide useful in utilizing endorepellin as an anti-angiogenic therapy in humans.