ABSTRACT
At the site of vessel injury, adhered platelets secrete both positive and negative regulators of angiogenesis, mainly from internal -granules. These positive regulators include: vascular endothelial growth factor-A (VEGF-A), VEGF-C, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), angiopoietin-1 (ANG1) insulin-like growth factor-1 and -2 (IGF-1,2), epidermal growth factor (EGF),
platelet-derived growth factor (PDGF), and sphingosine 1phosphate. One of the common themes is that the majority of the receptors for these factors belong to the tyrosine kinase receptor family (VEGFR flt1, KDR, PDGFR, HGFR, c-met, EGFR, c-erb1). One of the positive angiogenic regulators, hepatocyte growth factor, affects both stimulation and (via the generation of cryptic fragments) suppression of angiogenesis. In the bone marrow, the endothelial stem cells are regulated by G-CSF and their differentiation toward the endothelial linage is driven solely by this factor. A unique mitogen for endothelial cells, platelet-derived endothelial growth factor is actually a surface enzyme, thymidine phosphorylase.
