Intimal growth and neovascularization in human stenotic vein grafts

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Abstract
Myointimal thickening and microvessel ingrowth are commonly observed in vein graft stenosis, which complicates a third of infrainguinal bypass procedures. But a direct correlation between these two features has not been established. Our purpose was to analyze the relationship between neovascularity and intimal thickness in human vein grafts. Twenty-two explant stenotic vein grafts (STVG), 8 nonstenotic arterialized vein grafts (AVG), and 20 age-matched control greater saphenous veins (CGSV) were analyzed histologically and compared morphologically by light microscopy. Digitized computer image analysis was used to measure intimal thickness and quantitate microvessel ingrowth. Immunolocalization of endothelial cells around the lumen and in microvessels was determined using antibodies to factor VIII and to endothelial nitric oxide synthase (eNOS), respectively. Focal areas of endothelial disruption and thrombus deposition were present in 23% (5 of 22) of stenotic vein grafts. The neointima of STVG grafts was two- and fourfold thicker than that of AVG and CGSV, respectively (p < 0.0001). Microvessels were most frequently observed in the adventitia and media of STVG and increased in number with increasing intimal thickness (p < 0.001 by ANOVA). A fourfold increased neointimal thickness in critically stenotic vein grafts is associated with increased medial and adventitial neovascularization. Remodeling alone with doubling of the intimal thickness in nonstenotic arterialized vein grafts does not appear to be associated with enhancement of the graft microvasculature. More specific observations using an experimental model may allow us to further define the role of angiogenesis in vein graft stenosis and to determine the therapeutic implications of such observations.