Abstract 489: Ex vivo Porcine Coronary Artery Remodeling With Seeded Endothelial Cells

Coronary heart disease is the most common cardiovascular problem that causes 370,000 deaths in America annually. Replacing the diseased coronary artery with a conduit obtained from another part of the patients’ body is the gold standard for the current surgical interventions. The great saphenous veins are widely preferred as coronary bypass grafts since they are easy to harvest and can replace multiple arteries due to their abundance. However, the endothelial cells in saphenous vein lose their venous characteristics and cannot function properly, which causes frequent graft failure. Conversely, arterial grafts have higher patency rate due to better function of endothelium. Yet, arterial grafts are not abundantly available as saphenous veins. Tissue engineered blood vessels can potentially serve as an ample source for bypass conduits. However, small-diameter engineered vessels are also tending to fail without a healthy endothelium. Here we propose to investigate the potential of Sox17-overexpressing endothelial cells in the vessel lumens to prevent intimal hyperplasia. Sox17 expression leads to upregulation of arterial, anti-thrombotic and anti-inflammatory markers in endothelial cells. We used an ex-vivo porcine coronary artery model where we cultured the vessels in perfusion bioreactors to mimic arterial flow conditions. Our preliminary results show that the vessel wall injury, seeded endothelial cells and arterial shear acted synergistically on smooth muscle cell death in the media layer (Fig. 1). The present ex vivo vessel culture platform is a promising tool to study remodeling by isolating factors like endothelial cells, soluble and mechanical factors.