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资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。由于平滑肌细胞（SMC）生长，新内膜增生和壁增厚，大约30％的血管干预措施（例如移植物和支架）在很大程度上发生了肿瘤变窄和失败。虽然大多数研究都是针对预防新内膜增生的，但替代方法可能是刺激腔内变窄后刺激新内膜萎缩。我们已经证明，高血流量会诱导狒狒PTFE移植物中的新内膜萎缩，但没有在正常的动脉中。在今年完成的实验中，我们检验了以下假设：在存在炎症的情况下，血管萎缩需要壁张力损失，通过比较有或没有高血流量的狒狒乳ha动脉周围的松散和紧密的PTFE包裹。我们观察到动脉壁的显着萎缩，紧密包裹28天。在当前的实验中，我们将使用与DNA微阵列的减法抑制杂交（一种与标准微阵列方法相比非常低的丰度基因转录的基因转录的方法）来识别两种模型中萎缩过程中受调节的简短基因的简短列表（即，这些模型的植物和扭动的裂纹）是否明确（或者是薄的范围），是否表现出薄的范围（或者是在稀疏中都表现出来，均为渗透性，均为渗透性（或者均为稀疏）。动脉粥样硬化人颈动脉。我们还将通过定量糖胺聚糖和鉴定可能涉及基质损失的调节蛋白酶来确定狒狒新内膜萎缩是否涉及特定基质分子（尤其是蛋白聚糖versican）的丧失。