Vascular endothelial growth factors signalling in normal human dental pulp: a study of gene and protein expression

In the well-vascularized dental pulp vascular endothelial growth factor A (VEGF-A) is expressed. Vascular endothelial growth factor A is a member of the VEGF family, which includes VEGFs-B, -C, and -D. The latter three have not been investigated in the pulp. Vascular endothelial growth factors C and D are the only ligands for vascular endothelial growth factor receptor (VEGFR)-3, which is usually expressed in lymphatic endothelium. They can also activate VEGFR-2, the main angiogenic receptor. We aimed to study VEGFs signalling in human dental pulp at the gene level and to identify the cellular source for protein expression using immunolabelling. All VEGFs (-A, -B, -C, and -D) were expressed in the pulp and may exert both autocrine and paracrine effects in blood vessels and immune cells found to be equipped with VEGFRs-2 and -3. Lymphatic vessel endothelial hyaluronan receptor-positive macrophages, known to be involved in angiogenesis, were found in the pulp, whereas lymphatic vessels were not detected. Twenty-six of 84 VEGF signalling genes, including VEGFR-3, were expressed at a significantly higher level in the pulp than in the control periodontal ligament. In conclusion, the normal human pulp represents a tissue with relatively high VEGF signalling involving both immune responses and vascular activity.