Notch-1 signalling is activated in brain arteriovenous malformations in humans

Qichuan Zhuge, Ming Zhong, Weiming Zheng, Guo Yuan Yang, Xiaoou Mao, Lin Xie, Gourong Chen, Yongmei Chen, Michael T. Lawton, William L. Young, David A. Greenberg, Kunlin Jin

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that, compared with control brain vascular tissue, Notch-1 signalling was activated in smooth muscle and endothelial cells of the lesional tissue. Western blotting showed an activated form of Notch-1 in brain arteriovenous malformations, irrespective of clinical presentation and with or without preoperative embolization, but not in normal cerebral vessels from controls. In addition, the Notch-1 ligands Jagged-1 and Delta-like-4 and the downstream Notch-1 target Hes-1 were increased in abundance and activated in human brain arteriovenous malformations. Finally, increased angiogenesis was found in adult rats treated with a Notch-1 activator. Our findings suggest that activation of Notch-1 signalling is a phenotypic feature of brain arteriovenous malformations, and that activation of Notch-1 in normal vasculature induces a pro-angiogenic state, which may contribute to the development of vascular malformations.

Original languageEnglish
Pages (from-to)3231-3241
Number of pages11
JournalBrain
Volume132
Issue number12
DOIs
StatePublished - 1 Dec 2009

Fingerprint

Arteriovenous Malformations
Brain
Vascular Malformations
Smooth Muscle Myocytes
Blood Vessels
Endothelial Cells
Western Blotting
Immunohistochemistry
Ligands

Keywords

  • AVM
  • Angiogenesis
  • Brain
  • Human
  • Notch-1
  • Signalling

Cite this

Zhuge, Q., Zhong, M., Zheng, W., Yang, G. Y., Mao, X., Xie, L., ... Jin, K. (2009). Notch-1 signalling is activated in brain arteriovenous malformations in humans. Brain, 132(12), 3231-3241. https://doi.org/10.1093/brain/awp246
Zhuge, Qichuan ; Zhong, Ming ; Zheng, Weiming ; Yang, Guo Yuan ; Mao, Xiaoou ; Xie, Lin ; Chen, Gourong ; Chen, Yongmei ; Lawton, Michael T. ; Young, William L. ; Greenberg, David A. ; Jin, Kunlin. / Notch-1 signalling is activated in brain arteriovenous malformations in humans. In: Brain. 2009 ; Vol. 132, No. 12. pp. 3231-3241.
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Zhuge, Q, Zhong, M, Zheng, W, Yang, GY, Mao, X, Xie, L, Chen, G, Chen, Y, Lawton, MT, Young, WL, Greenberg, DA & Jin, K 2009, 'Notch-1 signalling is activated in brain arteriovenous malformations in humans', Brain, vol. 132, no. 12, pp. 3231-3241. https://doi.org/10.1093/brain/awp246

Notch-1 signalling is activated in brain arteriovenous malformations in humans. / Zhuge, Qichuan; Zhong, Ming; Zheng, Weiming; Yang, Guo Yuan; Mao, Xiaoou; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin.

In: Brain, Vol. 132, No. 12, 01.12.2009, p. 3231-3241.

Research output: Contribution to journalArticle

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Zhuge Q, Zhong M, Zheng W, Yang GY, Mao X, Xie L et al. Notch-1 signalling is activated in brain arteriovenous malformations in humans. Brain. 2009 Dec 1;132(12):3231-3241. https://doi.org/10.1093/brain/awp246