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Neointimal hyperplasia, transplant rejection and thus immunogenicity of allografts are possible reasons for poorer patency rates in cryopreserved venous allografts for peripheral bypass surgery in comparison with autologous venous grafts. To expand the limited knowledge from human allografts, we histologically investigated allogeneic and autologous venous grafts in arterial location. Specimens of allogeneic and autologous venous graft stenosis, harvested 6 months after bypass implantation, were immunohistochemically characterized. Examination of the lesions showed a uniform morphological pattern. A continuous endothelial layer, tissue fibrosis and a thickened neointima with monocytes and dedifferentiated vascular smooth muscle cells were seen in both conduits with very low cell turnover and the absence of acute and chronic inflammation. Neoangiogenesis with CD34-positive endothelium was abundant in the vessel media. The morphological patterns of allogeneic and autologous neointima formation are similar. Consequently, neointimal hyperplasia in venous grafts may reflect a uniform physiological host response of non-immunological factors with the reasons for poorer clinical outcome of cryopreserved allografts yet to be elucidated. [ABSTRACT FROM AUTHOR]

Endostatin decreased vascular endothelial growth factor (VEGF)-induced formation of endothelial tubes and microvessels sprouting from aortic rings and blocked their network. After cessation of treatment, the survival time of endostatin plus VEGF-treated tubes was approximately doubled in comparison to VEGF alone. Endostatin antibody blocked VEGF-induced endothelial tube formation and disrupted existing tubes. Endostatin immunostaining was localized between endothelium and basement membrane and in inter-endothelial junctions of new, but not of quiescent, blood vessels. In tumors grown in SCID mice, endostatin immunostaining was stronger accompanying blood vessel maturation and was significantly prominent in vessels of tumor marginal zone where angiogenesis is highly active. These data indicate a new antiangiogenic action of endostatin stabilizing and maturating endothelial tubes of newly formed blood vessels. Thus, strategies accelerating vascular stabilization and maturation could be promising in tumor therapy. [ABSTRACT FROM AUTHOR]

The high degree of vascularisation, accompanied by the low malignancy of human Leydig cell tumours, offers an interesting model to study the neovascularisation and structural stabilisation of the vascular wall. We report here that Leydig cell tumours are characterised by an increased level of vascular endothelial growth factor (VEGF) in testicular veins, the presence of VEGF mRNA and of its receptor, KDR, and an absence of detectable VEGF receptor Flt-1, in blood vessels of tumour marginal zones and of peri-tumour areas. This is in contrast to the capillaries within normal Leydig cell clusters which demonstrate both Flt-1 and KDR. Ultrastructural destabilisation of the vascular wall, evident as a lack of basement membrane and of peri-endothelial cells was also present in nearly 85% of blood vessels of the peri-tumour areas. In contrast, ≈89% of the blood vessels of the tumour centre region demonstrated a stabilised vascular wall including basement membrane and peri-endothelial cells. Local application of VEGFath> to the normal testicular tissue induced significant ultrastructural destabilisation in the capillary walls which only expressed KDR. These results suggest an autocrine role of VEGF on endothelial cells of tumour blood vessels in a region-specific manner and implicate that VEGF interactions with KDR, in the absence of Flt-1, may be involved in vascular destabilisation. In addition, the finding that most (79%) of Leydig tumour blood vessels are stabilised may account for the low malignant potential of these tumours. [ABSTRACT FROM AUTHOR]