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Therapeutic lymphangiogenesis with human recombinant VEGF‐C
Author(s) -
Szuba Andrzej,
Skobe Mihaela,
Karkkainen Marika J.,
Shin William S.,
Beynet David P.,
Rockson Ned B.,
Dakhil Noma,
Spilman Stan,
Goris Michael L.,
Strauss H. William,
Quertermous Thomas,
Alitalo Kari,
Rockson Stanley G.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0401fje
Subject(s) - lymphangiogenesis , lymphatic system , lymphedema , medicine , lymphatic vessel , vascularity , pathology , vascular endothelial growth factor c , lymphatic endothelium , vascular endothelial growth factor , vegf receptors , metastasis , breast cancer , cancer , vascular endothelial growth factor a
Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR‐3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF‐C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 μg dose of VEGF‐C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7–8 days following treatment. After VEGF‐C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF‐C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF‐C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.