Abstract 5119: Von Willebrand Factor is Expressed Differently in Pathological Angiogenesis Models and Potentially Mediates Angiogenesis
The objectives of this study were to assess von Willebrand factor (vWF) expression in different in vivo angiogenesis models, and also to investigate whether vWF plays a role in the regulation of angiogenesis. Basement membrane vWF is widely used as an endothelial cell marker for the analysis of physiological and pathological angiogenesis. In this study, we measured vWF expression in tumor xenografts, ischemic muscle, wound skin and matrigel implants. CD31 antibody, another routinely used endothelial cell marker, was used as an internal control. The sections of different tissues were immunofluorescently stained for vWF and CD31. The top five fields with the most microvessels in each section were acquired. The vWF- and CD31-positive vascular areas were quantified using Image-Pro Plus software and the ratios of vWF-/CD31-positive areas were compared. The ratios in normal muscle, skin and liver were 21.66%, 22.75% and 27.59%, respectively. In ischemic muscle and wound skin, the vWF/CD31 ratios were 23.10% and 21.73%, respectively, which were comparable with those in normal tissues. Matrigel implants had the highest ratio of vWF/CD31 (41.61%). However, tumor xenografts had the lowest ratios of vWF/CD31, which were 3.51% and 5.37% in breast cancer and melanoma, respectively. These data suggested that vWF expression is mediated by the micro-environment of distinct pathological processes. They also implied that the decreased expression of vWF in tumor vasculature might be a potential regulator of tumor growth and angiogenesis. We injected melanoma cells subcutaneously into wild type (WT) and vWF-deficient (vWF−/−) mice to examine tumor growth and vascular formation. Interestingly, the weight of tumors grown in vWF−/− mice was four times higher than that in WT counterparts. Importantly, the vascular area in the tumors from vWF−/− mice was significantly larger than that from the WT littermates. Taken together, these data demonstrate that vWF expression is different in distinct pathological angiogenesis models. Therefore, caution should be taken when using vWF as a vascular marker in different pathological angiogenesis models. Moreover, the decreased expression or deficiency of vWF might be implicated in the promotion of angiogenesis.
This research has received full or partial funding support from the American Heart Association, National Center.