The Effect of Stress-Induced Senescence on Aging Human Cord Blood-Derived Endothelial Cells

TitleThe Effect of Stress-Induced Senescence on Aging Human Cord Blood-Derived Endothelial Cells
Publication TypeJournal Article
Year of Publication2013
AuthorsCheung, TM, Ganatra, MP, Fu, JJ, and Truskey, GA
JournalCardiovascular Engineering and Technology
Start Page220
Pagination220 - 230
Date Published01/2013

We sought to determine the effect of stress-induced senescence on the permeability to albumin of aging endothelial progenitor cells. Human umbilical cord blood derived endothelial cells (hCB-ECs) and human aortic endothelial cells (HAECs) were treated with 200 μM H2O2 and permeability to FITC-bovine serum albumin was measured. Some samples were subsequently treated with 100 μM 8-pCPT-2′-O-Me-cAMP, a cAMP analog that activates the Epac1-Rap1 pathway. Cell proliferation was measured with the EdU assay. Phase contrast, and immunofluorescence images were taken to observe morphological changes in cells after exposure to H2O2. hCB-ECs exposed to H2O2 exhibited a significant increase in permeability, but their response differed from the HAECs. Low passage hCB-ECs had a permeability increase of about 82% (p < 0. 01) compared to aged cells which had a permeability increase of about 37% (p < 0. 05). This increase in permeability was reduced by treating the cells with 100 μM 8-pCPT-2′-O-Me-cAMP. The younger cells exhibited a significant decrease in proliferation after being subjected to various concentrations of H2O2 whereas the aged cells exhibited a more gradual decrease in the percent of cells in S-phase. These changes also correlated with changes in cell morphology and junction staining. When placed back in the original media, the morphology and permeability of the hCB-ECs returned to the control condition, while the HAECs did not. The permeability of low and high passage hCB-ECs and HAECs initially increases in response to oxidative stress. hCB-ECs, but not HAECs, were able to recover from the stress 24 h later. Early passage hCB-ECs were more susceptible to exogenous H2O2 than late passage hCB-ECs. The increase in permeability of hCB-ECs to H2O2 also correlated with decreased cell proliferation and changes in cell junctions. © 2013 Biomedical Engineering Society.

Short TitleCardiovascular Engineering and Technology