Transgenic rabbits with increased VEGF expression develop hemangiomas in the liver: a new model for Kasabach–Merritt syndrome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-10-03

AUTHORS

Shuji Kitajima, Enqi Liu, Masatoshi Morimoto, Tomonari Koike, Ying Yu, Teruo Watanabe, Shigehiko Imagawa, Jianglin Fan

ABSTRACT

Clinical studies have provided ample evidence that high (either systemic or local) levels of vascular endothelial growth factor (VEGF) are associated with several pathophysiological disorders, including hemangiomas. To investigate whether elevated VEGF expression could directly affect these disorders, we created a transgenic (Tg) rabbit model with increased hepatic expression of the human VEGF165 transgene under the control of the human α-antitrypsin promoter. Tg rabbits exhibited marked hepatomegaly, with livers 2.5-fold heavier than those of control rabbits. Histological analysis revealed that the livers of Tg rabbits showed prominent dilation of the sinusoids and formed various-sized blood vessel networks, a feature of diffuse hemangiomas. Immunohistochemical staining revealed that the hepatocytes produced VEGF165, whereas plasma VEGF165 was not detected. Furthermore, Tg rabbits suffered from hemolytic anemia, thrombocytopenia and splenomegaly, which was associated with marked extramedullary hematopoiesis. The manifestations of Tg rabbits mimic many of the features of hemangiomatous disorders in humans such as the Kasabach–Merritt syndrome, and therefore this model may be potentially useful for the study of the pathogenesis and complications of hemangiomas as well as the investigation of angiogenesis inhibitors. More... »

PAGES

1517-1527

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/labinvest.3700346

DOI

http://dx.doi.org/10.1038/labinvest.3700346

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008150879

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16200077


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