Abstract 12675: Endothelial Cell Behaviour in Response to Des Drugs Shows Significant Species Differences: A Comparison of Human, Swine and Rabbit Endothelium
Drug Eluting Stents (DES) have been reported to increase the incidence of late stent thrombosis (LST). For its association with non-covered struts, delayed endothelial cell (EC) regrowth has been proposed as the main cause for LST. Preclinical studies report contradicting results as DES do not delay EC regrowth in all models. Stenting of denuded rabbit iliac arteries shows delayed EC regrowth and is suggested to better represent human coronary stenting than porcine coronary arteries. Differences between models are the basis for difficulties in interpreting and comparing results and stem from methodology (direct stenting vs. prior denudation) and species differences (rabbit vs. pig). We therefore assessed species differences in EC behaviour of proliferation (population doubling times) and EC monolayer woundhealing (scratch assay) subjected to DES-drugs.
Methods. We determined dose response curves (0; 0.1; 10; 1000nM) to Paclitaxel (P) and Everolimus (E) in Porcine and human Coronary Artery EC (PCAEC, HCAEC) and Rabbit Aortic EC (RAEC) for 1) proliferation and 2) woundhealing.
Results. 1) RAEC proliferated faster and were significantly less sensitive to P than HCAEC (p=0.02). No differences were found between HCAEC and PCAEC (p=1.0). RAEC were also significantly less sensitive to E than HCAEC (p=0.01) as well as PCAEC (p=0.01). Again, no significant difference was found between HCAEC and PCAEC (p=1). 2) RAEC, PCAEC and HCAEC all responded significantly different to wounding in presence of p (p<0.001). RAEC healed fastest and was least sensitive, HCAEC grew slowest and was most sensitive to P. E showed a similar difference between RAEC, PCAEC and HCAEC (p<0.001), again with RAEC showing the least and HCAEC the highest sensitivity to the drug. As a control for vascular bed effects, we compared porcine coronary and aortic EC. As behaviour was identical, cell culture differences were attributed to species- rather than vascular bed differences.
Conclusion. Human coronary EC behaviour and drug sensitivity is more similar to Porcine coronary EC than Rabbit aortic EC regarding proliferation and wound healing in vitro. These differences are attributable to species differences rather than vascular bed differences.
- © 2011 by American Heart Association, Inc.