Abstract
Background. Autotransplantation of parathyroid tissue after parathyroidectomy is successful at
salvaging parathyroid function. The relatively high success of parathyroid transplantation
is thought to be due, in part, to the ability of parathyroid tissue to induce angiogenesis
and thus recruit a new vasculature. Vascular endothelial growth factor (VEGF) is a
potent angiogenic factor produced by a number of tumors and hypoxic tissues. Using
a 3-dimensional intact microvessel angiogenesis system, we evaluated the role of VEGF
in the stimulation of angiogenesis by human parathyroid cells. Methods. Freshly isolated rat microvessels embedded in a 3-dimensional collagen I matrix were
treated with healthy 1-mm3 fragments of human parathyroid tissue or isolated parathyroid cells. Other gels were
supplemented with VEGF165 or FLT-1 soluble receptor fusion protein to bind VEGF. After 11 days 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 parathyroid coculture (8.4
± 1.0 mm) versus VEGF165 supplemented gels (6.2 ± 0.3 mm, P <.01). VEGF165 significantly augmented parathyroid-stimulated angiogenesis (13.7 ± 2.4 mm, P <.05 vs parathyroid alone). Using quantitative reverse transcriptase-polymerase chain
reaction, we identified VEGF messenger RNA (mRNA) induction within 1 hour of parathyroid
explant, with a 12-fold increase by 24 hours. Treatment of parathyroid cocultures
with 0.2 μg/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 model. However, our data suggests that other
parathyroid-produced factors are involved in mediating parathyroid-induced angiogenesis.
(Surgery 2000;128:458–64)
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Article info
Publication history
Accepted:
March 11,
2000
Footnotes
*Supported by a research grant from the Eastern Virginia Medical School Foundation (Grant 867850).
**Reprint requests: W. Bradford Carter, MD, Division of Surgical Oncology, Department of Surgery, University of Maryland, 22 S Greene St, 54B14, Baltimore, MD 21201.
*Surgery 2000;128:458–64.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
