Prim David A, Menon Vinal, Hasanian Shahd, Carter Laurel, Shazly Tarek, Potts Jay D, Eberth John F
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, USA.
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA.
J Vasc Res. 2018;55(5):255-267. doi: 10.1159/000492484. Epub 2018 Sep 4.
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 then evaluated samples acutely (6 h) and chronically (7 days) under in situ or coronary-like perfusion conditions. Although morphologically similar, primary cells harvested from the ITA illustrated lower intimal and medial, but not adventitial, cell proliferation rates than those from the RA or GSV. Basal gene expression levels were similar in all vessels, with only COL3A1, SERPINE1, FN1, and TGFB1 being 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 in situ. Many of the remodeling genes perturbed at 6 h were restored after 7 days (COL3A1, FN1, MMP2, and TIMP1) while others (SERPINE1, TGFB1, and VCAM1) were not. The findings elucidate the potential mechanisms of graft failure and highlight strategies to encourage healthy ex vivo pregraft conditioning.
适应性重塑过程对于冠状动脉搭桥移植物的维持和存活至关重要，临床结果在很大程度上取决于组织来源。在本研究中，我们利用体外灌注生物反应器培养常见人类搭桥移植物的猪类似物：胸廓内动脉（ITA）、桡动脉（RA）和大隐静脉（GSV），然后在原位或冠状动脉样灌注条件下对样本进行急性（6小时）和慢性（7天）评估。尽管形态相似，但从ITA收获的原代细胞的内膜和中膜细胞增殖率低于从RA或GSV收获的细胞，而外膜细胞增殖率则无差异。所有血管的基础基因表达水平相似，仅COL3A1、SERPINE1、FN1和TGFB1在培养前存在差异表达；然而，所有基因中有超过一半在名义上受到培养过程的影响。当暴露于冠状动脉样条件时，RA和GSV经历了ITA或在原位研究血管时不存在的病理重塑。许多在6小时时受到干扰的重塑基因在7天后恢复（COL3A1、FN1、MMP2和TIMP1），而其他基因（SERPINE1、TGFB1和VCAM1）则未恢复。这些发现阐明了移植物失败的潜在机制，并突出了促进健康的体外移植前预处理的策略。
