MECHANISMS OF ARTERIAL GRAFT HEALING

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大约30%的血管介入（例如，移植物和支架）发生管腔狭窄，并且主要由于平滑肌细胞（SMC）生长、新生内膜增生和壁增厚而失败。虽然大多数研究都是针对预防新生内膜增生，但另一种选择可能是在管腔狭窄发生后刺激新生内膜萎缩。我们已经证明，高血流量诱导狒狒PTFE移植物的新生内膜萎缩，但不是在正常髂动脉。在今年完成的一项实验中，我们通过比较狒狒髂动脉周围有和没有高血流量的松和紧PTFE包裹来测试血管萎缩需要在炎症存在下失去壁张力的假设。我们观察到28天的动脉壁与紧密包裹显着萎缩。在当前的实验中，我们将使用DNA微阵列的消减抑制杂交（一种与标准微阵列方法相比鉴定丰度极低基因的基因转录的方法）来鉴定在两种模型中在萎缩期间受到调控的基因的短列表（即移植新生内膜和包裹的动脉），然后确定这些基因是否表达在狭窄的动脉粥样硬化的人颈动脉的变薄的纤维帽中，我们还将确定狒狒新生内膜萎缩是否涉及特定基质分子（特别是蛋白聚糖多功能蛋白聚糖）的损失，通过定量糖胺聚糖和鉴定可能参与基质损失的受调节蛋白酶。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 30% of vascular interventions (for example, grafts and stents) develop lumenal narrowing and fail largely as a result of smooth muscle cell (SMC) growth, neointimal hyperplasia, and wall thickening. While most research has been directed at preventing neointimal hyperplasia, an alternative might be to stimulate neointimal atrophy after lumenal narrowing has developed. We have demonstrated that high blood flow induces neointimal atrophy in baboon PTFE grafts, but not in the normal iliac artery. In an experiment completed this year, we tested the hypothesis that vascular atrophy requires a loss of wall tension in the presence of inflammation by comparing loose and tight PTFE wraps around baboon iliac artery with and without high blood flow. We observed significant atrophy of the arterial wall with the tight wraps for 28 days. In a current experiment, we will use subtractive suppressive hybridization with DNA microarrays (a method that identifies gene transcription of very low abundance genes compared to standard microarray methods) to identify a short list of genes that are regulated during atrophy in both models (i.e. graft neointima and wrapped artery) and will then determine whether these genes are expressed (or repressed) in the thinning fibrous cap of stenotic atherosclerotic human carotid arteries. We will also determine whether baboon neointimal atrophy involves the loss of specific matrix molecules (especially the proteoglycan versican) by quantitating glycosaminoglycans and identifying regulated proteases possibly involved in matrix loss.