Evaluation of human endothelial cells post stent deployment in a cardiovascular simulator in vitro.
Percutaneous stent implantation has revolutionized the clinical treatment of occluded arteries. Nevertheless, there is still a large unmet need to prevent re-occlusion after implantation. Consequently, a niche exists for a cost-effective pre-clinical method of evaluating novel interventional devices in human models. Therefore, the development of a coronary model artery offers tremendous potential for the treatment of endothelial cell dysfunction and restenosis. As a first step, we employ tissue-engineering principles to examine the effect of stent deployment upon endothelial cells in a tubular in vitro system capable of replicating the coronary artery biomechanical environment. In particular, the cellular and molecular changes pertaining to inflammation, proliferation, and death were assessed after stent deployment. Real-time quantitative PCR demonstrated increased expression of genes encoding for E-Selectin, ICAM-1, and VCAM-1; markers associated with an inflammatory response in vivo. Further, an increase in the pro-apoptotic protein Bax was paralleled with a decrease in the anti-apoptotic protein Bcl-2; however, apoptotic morphology was not observed. Interestingly, transcription of c-fos increased, whereas Ki67 levels fell over the same period. One hypothesis is that these results are in response to the altered local hemodynamic environment induced by stent deployment. Most significantly, this study highlights the potential of a biomimetic hemodynamic bioreactor combined with a gene expression analysis to evaluate, with greater specificity, the performance and interaction of stents with the endothelial layer in a controlled environment.
Punchard
Marie A
MA
National Centre for Biomedical Engineering, Orbsen Building, National University of Ireland, Galway, University Road, Galway, Ireland.
O'Cearbhaill
Eoin D
ED
Mackle
Joseph N
JN
McHugh
Peter E
PE
Smith
Terry J
TJ
Stenson-Cox
Catherine
C
Barron
Valerie
V
D040761:Biomimetic Materials; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000209:etiology / Q000276:immunology; D003331:Coronary Vessels / Q000276:immunology* / Q000601:surgery*; D016207:Cytokines / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D019544:Equipment Failure Analysis / Q000295:instrumentation / Q000379:methods; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000276:immunology; D006801:Humans; D015607:Stents / Q000009:adverse effects*; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods
D016207:Cytokines