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Endogenous hormone 2‐methoxyestradiol suppresses venous hypertension‐induced angiogenesis through up‐ and down‐regulating p53 and id‐1.
- Source :
- Journal of Cellular & Molecular Medicine; Feb2018, Vol. 22 Issue 2, p957-967, 11p
- Publication Year :
- 2018
-
Abstract
- Abstract: Brain arteriovenous malformations (AVMs) which associate with angiogenesis due to local hypertension, chronic cerebral ischaemia and tissue hypoxia usually lead to haemorrhage, however, the therapeutic medicine for the disease is still lacking. 2‐methoxyestradiol (2‐ME) has been shown effective in the anti‐angiogenic treatment. This study was conducted to examine whether and how 2‐ME could improve the vascular malformations. Intracranial venous hypertension (VH) model produced in adult male Sprague‐Dawley rats and culture of human umbilical vein endothelial cells (HUVECs) at the anoxia condition were used to induce <italic>in vivo</italic> and <italic>in vitro</italic> angiogenesis, respectively. Lentiviral vectors of <italic>ID‐1</italic> and <italic>p53</italic> genes and of their <italic>siRNA</italic> were intracranially injected into rats and transfected into HUVECs to overexpress and down‐regulate these molecules. 2‐ME treatment not only reduced the <italic>in vivo</italic> progression of brain tissue angiogenesis in the intracranial VH rats and the <italic>in vitro</italic> increases in microvasculature formation, cellular migration and HIF‐1α expression induced by anoxia in HUVECs but also reversed the up‐regulation of ID‐1 and down‐regulation of p53 in both the <italic>in vivo</italic> and <italic>in vitro</italic> angiogenesis models. All of the anti‐angiogenesis effects of 2‐ME observed in VH rats and anoxic HUVECs were abrogated by ID‐1 overexpression and p53 knockdown. Our data collectively suggest that 2‐ME treatment inhibits hypoxia/anoxia‐induced angiogenesis dependently on ID‐1 down‐regulation and p53 up‐regulation, providing a potential alternative medical treatment for un‐ruptured AVM patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15821838
- Volume :
- 22
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Cellular & Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 127562930
- Full Text :
- https://doi.org/10.1111/jcmm.13399