MECHANISMS OF ARTERIAL GRAFT HEALING

动脉移植物愈合机制

• 批准号: 7349383
• 负责人: ALEXANDER W CLOWES
• 金额: $ 9.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349383
• 关键词: MECHANISMS; ARTERIAL; GRAFT; HEALING

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。大约 30% 的血管介入治疗（例如移植物和支架）会出现管腔狭窄并失败，这主要是由于平滑肌细胞 (SMC) 生长、新内膜增生和管壁增厚造成的。虽然大多数研究都是针对预防新内膜增生，但另一种选择可能是在管腔变窄后刺激新内膜萎缩。我们已经证明，高血流量会引起狒狒 PTFE 移植物的新生内膜萎缩，但不会引起正常髂动脉的新生内膜萎缩。在今年完成的一项实验中，我们通过比较有和没有高血流量的狒狒髂动脉周围松散和紧密的 PTFE 包裹，检验了血管萎缩需要在炎症存在的情况下失去壁张力的假设。紧密包裹 28 天后，我们观察到动脉壁明显萎缩。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识别非常低丰度基因的基因转录的方法）来识别在两种模型中萎缩期间受到调节的基因的简短列表（即移植物）新内膜和包裹动脉），然后确定这些基因是否在狭窄动脉粥样硬化人类颈动脉的变薄纤维帽中表达（或抑制）。我们还将通过定量糖胺聚糖并鉴定可能与基质损失有关的调节蛋白酶来确定狒狒新生内膜萎缩是否涉及特定基质分子（尤其是蛋白聚糖多功能蛋白聚糖）的损失。