MECHANISMS OF ARTERIAL GRAFT HEALING

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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.