Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain

Yiqian Zhu, Ileana C. Cuevas, Rodney Allanigue Gabriel, Hua Su, Stephen Nishimura, Peng Gao, Alexander Fields, Qi Hao, William L. Young, Guo Yuan Yang, Nancy J. Boudreau

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Hemangiomas are angiogenesis-dependent benign vascular tumors that can rupture and cause intracranial hemorrhages. We previously showed that the transcription factor homeobox A5 (HoxA5), which is absent in activated angiogenic endothelial cells can block angiogenesis. Here, we investigated whether restoring expression of HoxA5 blocks hemangioma growth by transplanting mouse hemangioendothelioma endothelial cells (EOMA) or HoxA5-expressing EOMA cells into the brains of mice. The EOMA cells induced brain hemangiomas characterized by large cystlike spaces lined by thin walls of endothelial cells surrounded by scant smooth muscle cells. When HoxA5-expressing EOMA cells were injected, lesion volumes were reduced between 5- and 20-fold compared with the EOMA control group (p < 0.05). Restoration of HoxA5 was associated with increased thrombospondin-2, which inhibits angiogenesis and reduced hypoxia-inducible factor 1α expression. These data suggest that restoring HoxA5 can attenuate experimental brain hemangioma development.

Original languageEnglish (US)
Pages (from-to)626-632
Number of pages7
JournalJournal of neuropathology and experimental neurology
Volume68
Issue number6
DOIs
StatePublished - Jun 2009

Keywords

  • Angiogenesis
  • Brain
  • EOMA
  • Hemangioma
  • Homeobox A5
  • Mouse

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Zhu, Y., Cuevas, I. C., Gabriel, R. A., Su, H., Nishimura, S., Gao, P., Fields, A., Hao, Q., Young, W. L., Yang, G. Y., & Boudreau, N. J. (2009). Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain. Journal of neuropathology and experimental neurology, 68(6), 626-632. https://doi.org/10.1097/NEN.0b013e3181a491ce