Intimal growth and neovascularization in human stenotic vein grafts

Background: Myointimal thickening and microvessel ingrowth are commonly obs erved in vein graft stenosis, which complicates a third of infrainguinal by pass procedures. But a direct correlation between these two features has no t been established. Our purpose was to analyze the relationship between neo vascularity and intimal thickness in human vein grafts. Study Design: Twent y-two explant stenotic vein grafts (STVG), 8 nonstenotic arterialized vein grafts (AVG), and 20 age-matched control greater saphenous veins (CGSV) wer e analyzed histologically and compared morphologically by light microscopy. Digitized computer image analysis was used to measure intimal thickness an d quantitate microvessel ingrowth. Immunolocalization of endothelial cells around the lumen and in microvessels was determined using antibodies to fac tor VIII and to endothelial nitric oxide synthase (eNOS), respectively. Res ults: Focal areas of endothelial disruption and thrombus deposition were pr esent in 23% (5 of 22) of stenotic vein grafts. The neointima of STVG graft s 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 thick-ness ( p < 0.001 by ANOVA). Conclusions: A fourfold increased neointimal thickness in critically stenotic vein grafts is associated with increased medial and adventitial neovascularization. Remodeling alone with doubling of the inti mal thick- ness 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 th e role of angiogenesis in vein graft stenosis and to deter- mine the therap eutic implications of such observations.