Abstract
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including tumour vascularization. Our preliminary observations indicated higher VEGF concentrations in serum samples than in matched plasma samples. We have now demonstrated that this difference is due to the presence of VEGF within platelets and its release upon their activation during coagulation. In eight healthy volunteers, serum VEGF concentrations ranged from 76 to 854 pg ml(-1) and were significantly higher (P < 0.01) than the matched citrated plasma VEGF concentrations, which ranged from < 9 to 42 pg ml(-1). Using platelet-rich plasma, mean (s.d.) platelet VEGF contents of 0.56 (0.36) pg of VEGF 10(-6) platelets were found. Immunocytochemistry demonstrated the cytoplasmic presence of VEGF within megakaryocytes and other cell types within the bone marrow. From examination of the effects of blood sample processing on circulating VEGF concentrations, it is apparent that for accurate measurements, citrated plasma processed within 1 h of venepuncture should be used. Serum is completely unsuitable. The presence of VEGF within platelets has implications for processes involving platelet and endothelial cell interactions. e.g. wound healing, and in tumour metastasis, when platelets adhering to circulating tumour cells may release VEGF at points of adhesion to endothelium, leading to hyperpermeability and extravasation of cells.
Highlights
Angiogenesis, the formation of new blood vessels from an existing vasculature, is a complex multistep process involving degradation of extracellular matrix proteins and activation, proliferation and migration of endothelial cells and pericytes (Folkman and Shing, 1992; Diaz-Flores et al, 1994; Folkman, 1995). It plays a key role in physiological processes involving neovascularization, such as ovulation, placentation and embryogenesis, and is central to several pathological processes, such as tumour growth and metastasis
We report here the results of our further investigations, which clearly indicate the presence of vascular endothelial growth factor (VEGF) in megakaryocytes and its release from platelets, and make recommendations regarding optimal handling of biological samples for accurate measurement of VEGF
Serum and platelet-free plasma samples were prepared by centrifugation at 2000 g for 10 min and platelet-rich plasma (PRP) by centrifugation at 180 g for 10 min with removal of the upper 1 ml of plasma only
Summary
Angiogenesis, the formation of new blood vessels from an existing vasculature, is a complex multistep process involving degradation of extracellular matrix proteins and activation, proliferation and migration of endothelial cells and pericytes (Folkman and Shing, 1992; Diaz-Flores et al, 1994; Folkman, 1995). It plays a key role in physiological processes involving neovascularization, such as ovulation, placentation and embryogenesis, and is central to several pathological processes, such as tumour growth and metastasis. Several factors have been identified that have angiogenic activity, but one of the most potent and specific that has both angiogenic and vasculogenic activity is vascular endothelial growth factor (VEGF), known as vascular permeability factor (VPF) and vasculotropin (Dvorak et al, 1995; Ferrara et al, 1995; Thomas 1996)
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