Parathyroid-induced angiogenesis is VEGF-dependent

Background. Autotransplantation of parathyroid tissue after parathyroidecto my is successful at salvaging parathyroid function. The relatively high suc cess of parathyroid transplantation is thought to be due, in part, to the a bility of parathyroid tissue to induce angiogenesis and thus recruit a new vasculature. Vascular endothelial growth factor (VEGF) is a potent angiogen ic factor produced by a number of tumors and hypoxic tissues. Using a 3-dim ensional intact microvessel angiogenesis system, we evaluated the role of V EGF in the stimulation of angiogenesis by human parathyroid cells. Methods. Freshly isolated rat microvessels embedded in a 3-dimensional coll agen I matrix were treated with healthy 1-mm(3) fragments of human parathyr oid tissue or isolated parathyroid cells. Other gels were supplemented with VEGF(165) or FLT-1 soluble receptor fusion protein to bind VEGF. After 11 clays in culture, the gels were stained with Gs-1 lectin, a marker for rat endothelium, and linear growth of the microvessels was determined by using image analysis. Parathyroid production of VEGF was determined with reverse transcriptase-polymerase chain reaction. Results. A significant increase in microvessel growth was seen in parathyro id coculture (8.4 +/- 1.0 mm) versus VEGF(165) supplemented gels (6.2 +/- 0 .3 mm, P < .01). VEGF(165) significantly augmented parathyroid-stimulated a ngiogenesis (13.7 +/- 2.4 mm, P < .05 vs parathyroid alone). Using quantita tive reverse transcriptase-polymerase chain reaction we identified VEGF mes senger RNA (mRNA) induction within I hour of parathyroid explant, with a 12 -fold inn-ease by 24 hours. Treatment of parathyroid cocultures with 0.2 mu g/mL FLT-1 soluble receptor protein completely eliminated the parathyroid induction of angiogenesis. Conclusions. Parathyroid tissue expresses low levels of VEGF mRNA, which is significantly upregulated on explantation. Furthermore, the increased VEGF expression is essential to drive parathyroid-induced angiogenesis in our m odel. However; our data suggests that other parathyroid-produced factors al e involved in mediating parapathyroid-induced angiogenesis.