Abstract
Angiogenesis is a critical determinant of tumor growth and the development of metastases. Heparin, steroids, and heparin/steroid combinations have been used in a variety of in vitro models and in vivo in animal models as effective inhibitors of angiogenesis. We tested heparin, steroid and heparin/steroid combinations at a variety of concentrations to determine their effect on the human ‘angiogenic switch’ from a resting to a proliferative endothelium in vessels from three placentas (initiation), and the effect of these compounds on the subsequent growth of a human angiogenic response (promotion). Using full-thickness human placental vein discs cultured in three-dimensional fibrin-thrombin clots, we demonstrated that heparin (300, 3000 μg/ml), steroid (350, 3500 μg/ml), and combinations of heparin/steroid at these doses effectively blocked both initiation and promotion of a human angiogenic response in a dose-dependent fashion. We also demonstrated that high-dose steroid or heparin/steroid treatment for 15 days resulted in disruption of vessel integrity, while treatment with heparin alone produced a suppressed growth rate but had intact vessel architecture. High-dose heparin/steroid treatment could also disrupt a developed angiogenic response and retard further development of an angiogenic response following the cessation of treatment.
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Jung, S.P., Siegrist, B., Wade, M.R. et al. Inhibition of human angiogenesis with heparin and hydrocortisone. Angiogenesis 4, 175–185 (2001). https://doi.org/10.1023/A:1014089706107
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DOI: https://doi.org/10.1023/A:1014089706107