EFFECT OF IMPROVED GRAFT COMPLIANCE MATCHING ON INTIMAL HYPERPLASIA

 描述：生物活性、生物稳定的移植物有可能取代病变的小口径血管，而不会出现与自体或当前合成移植物相关的并发症。“现成”血管移植物发展的一个主要障碍是由于内膜增生(IH)导致移植物再闭塞的可能性。在移植物顺应性和长期通畅性之间存在着很强的经验相关性。因此，合规已被确定为“现成”移植成功的关键决定因素。尽管有这种强烈的经验相关性，但还没有权威的研究证明，具有更好的顺应性匹配的合成移植物确实具有与自体移植物相似的性能。此外，合规不匹配将导致IH的机制相对较少。因此，问题仍然是-合规性是否足够匹配，如果是的话，为什么？在拟议的研究中，我们将首先在已建立的IH体外器官培养模型中评估包含不同顺应性的缝合移植物的猪颈动脉。这些体外研究将有助于识别 早期EC、巨噬细胞和SMC标记物与移植物顺应性改变相关。然后，我们将使用猪模型证实，细胞表型的类似变化与体内IH的形成程度相关。完成后，拟议的研究将：1)验证IH用于筛选血管移植物的短期器官培养模型；2)提供与移植物相关的数据 顺应性和导致IH的早期细胞表型变化；3)评估通过限制IH改善顺应性匹配减少移植物再闭塞的程度。总体而言，这些结果将使小口径血管假体的改进设计成为可能，并将验证评估移植物对IH抵抗的快速体外筛查工具。未来的研究将利用这一模型。 探讨移植物诱导的间质纤维化的潜在机制。

 DESCRIPTION: Bioactive, biostable grafts have the potential to replace diseased small-caliber vessels without the complications associated with autologous or current synthetic grafts. A major roadblock in 'off-the-shelf' vascular graft development is the potential for graft re- occlusion due to intimal hyperplasia (IH). A strong empirical correlation exists between graft compliance and long term patency. As such, compliance has been identified as a key determinant of 'off the shelf' graft success. Despite this strong empirical correlation, there has not been a definitive study to demonstrate that a synthetic graft with improved compliance matching does indeed perform similar to an autograft. In addition, the mechanisms by which compliance mismatch would lead to IH are relatively poorly understood. So, the question remains - is compliance matching enough, and if so, why? In the proposed studies, we will first evaluate porcine carotid arteries containing sutured grafts of various compliance values in an established ex vivo organ culture model of IH. These ex vivo studies will aid in the identification of early EC, macrophage and SMC markers associated with alterations in graft compliance. We will then then confirm that similar alterations in cell phenotype are correlated with degree of IH formation in vivo using a porcine model. Upon completion, the proposed studies will: 1) validate a short term organ culture model of IH for screening vascular grafts; 2) provide data linking graft compliance and the early cell phenotypic changes that lead to IH; 3) evaluate the degree to which improved compliance-matching reduces graft re-occlusion by limiting IH. Overall, these results will enable improved design of small-caliber vascular prostheses and will validate a rapid ex vivo screening tool for assessing graft resistance to IH. Future studies will utilize this model to probe the underlying mechanisms that drive graft-induced IH.