Endothelial cell growth: biology and pharmacology in relation to angiogenesis

The vascular system is lined by a monolayer of endothelial cells which proliferate very slowly under normal conditions. The formation of new capillary vessels is associated with some physiological circumstances and several pathological conditions. Angiogenesis requires migration, differentiation and proliferation of endothelial cells. The mechanism of tube formation is still poorly understood. Tumour growth is angiogenesis-dependent and angiogenesis is directly or indirectly induced by the tumour. Induction of angiogenesis is an important step in carcinogenesis and in metastatic development. Angiogenesis is induced during the transition from hyperplasia to neoplasia. Numerous angiogenic factors have been identified, most are mitogenic for endothelial cells and some are only responsible for tube formation. However, it is difficult to recognize which factor is the most important in vivo. Since angiogenesis is necessary for tumour growth, any natural or synthetic antiangiogenic compound may have an antineoplastic potential. Inhibition of tumour angiogenesis under the control of a tumour suppression gene could play an important role. Pharmacological compounds, such as heparin, heparin fragments and corticosteroids, have been shown to be antiangiogenic substances. More recently two new inhibitors of capillary endothelial cell proliferation and/or angiogenesis have been described: they are a cartilage-derived inhibitor and platelet factor 4.