Perfusion Tissue Culture Initiates Differential Remodeling of Internal Thoracic Arteries Radial Arteries and Saphenous Veins

摘要

Adaptive remodeling processes are essential to the maintenance and viability of coronary artery bypass grafts where clinical outcomes depend strongly on the tissue source. In this investigation, we utilized an ex vivo perfusion bioreactor to culture porcine analogs of common human bypass grafts: the internal thoracic artery (ITA), the radial artery (RA), and the great saphenous vein (GSV), and evaluated samples acutely (6 hours) and chronically (7 days) under in situ or coronary-like perfusion conditions. Although morphologically similar, primary cells harvested from ITAs illustrated lower intimal and medial, but not adventitial, cell proliferation rates compared to RAs or GSVs. Basal gene expression levels were similar between all vessels with only COL3A1, SERPINE1, FN1 and TGFB1 differentially expressed prior to culture; however, over half of all genes were affected nominally by the culturing process. When exposed to coronary-like conditions, RAs and GSVs experienced pathological remodeling not present in ITAs or when vessels were studied under their in situ conditions. Many of the remodeling genes perturbed at 6 hours were restored after 7 days (COL3A1, FN1, MMP2, TIMP1) while others (SERPINE1, TGFB1, VCAM1) were not. Findings elucidate potential mechanisms of graft failure and highlight strategies to encourage healthy ex vivo pre-graft conditioning.