Dataset Information

Endogenous hormone 2-methoxyestradiol suppresses venous hypertension-induced angiogenesis through up- and down-regulating p53 and id-1.

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 in vivo and in vitro angiogenesis, respectively. Lentiviral vectors of ID-1 and p53 genes and of their siRNA were intracranially injected into rats and transfected into HUVECs to overexpress and down-regulate these molecules. 2-ME treatment not only reduced the in vivo progression of brain tissue angiogenesis in the intracranial VH rats and the in vitro increases in microvasculature formation, cellular migration and HIF-1? expression induced by anoxia in HUVECs but also reversed the up-regulation of ID-1 and down-regulation of p53 in both the in vivo and in vitro 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.

SUBMITTER: Zou X

PROVIDER: S-EPMC5783857 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Endogenous hormone 2-methoxyestradiol suppresses venous hypertension-induced angiogenesis through up- and down-regulating p53 and id-1.

Zou Xiang X Zhang Li L Yuan Jie J Yang Chunjie C Wu Zehan Z Song Jianping J Zhu Wei W Mao Ying Y Chen Liang L

Journal of cellular and molecular medicine 20171129 2

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 Spra ...[more]

PMID: 29193609

Similar Datasets

Project description:Background and aimsBy blocking TNF?-related effects, thalidomide not only inhibits hepatic fibrogenesis but improves peripheral vasodilatation and portal hypertension in cirrhotic rats. Nonetheless, the investigation of thalidomide's effects on splanchnic and collateral microcirculation has been limited. Our study explored the roles of intestinal and mesenteric TNF? along with inflammasome-related pathway in relation to cirrhosis and the splanchnic/collateral microcirculation.MethodsUsing in vivo and in vitro approaches, mechanisms of the effects of thalidomide on intestinal and mesenteric inflammatory, vasodilatory and angiogenic cascades-related abnormalities were explored in cirrhotic rats that had received 1-month thalidomide (C-T) treatment.ResultsIn cirrhotic rats, high tumor necrosis factor (TNF)?, vascular endothelial growth factor (VEGF) and nitric oxide (NO)x levels were associated with the NOD-like receptors protein 3 (NLRP3), IL-1? and caspase-1 inflammasome over-expression in splenorenal shunt and mesenteric tissues. The thalidomide-related inhibition of mesenteric and splenorenal shunt inflammasome expression was accompanied by a significantly decreased intestinal mucosal injury and inflammasome immunohistochemical staining expression. Suppression of various angiogenic cascades, namely VEGF-NOS-NO, was paralleled by a decrease in mesenteric angiogenesis as detected by CD31 immunofluorescence staining and by reduced portosystemic shunting (PSS) in C-T rats. The down-regulation of the mesenteric and collateral vasodilatory VEGF-NOS-NO cascades resulted in a correction of vasoconstrictive hypo-responsiveness and in an attenuation of vasodilatory hyper-responsiveness when analyzed by in situ perfusion of the superior mesenteric arterial (SMA) and portosystemic collaterals. There was also a decrease in SMA blood flow and an increase in SMA resistance in the C-T rats. Additionally, acute incubation with thalidomide abolished TNF?-augmented VEGF-mediated migration of and tube formation of human umbilical vein endothelial cells, which was accompanied by corresponding changes in inflammatory and angiogenic substances release.ConclusionsThe suppression of inflammasome over-expression by chronic thalidomide treatment ameliorates inflammatory, angiogenic and vasodilatory cascades-related pathogenic changes in the splanchnic and collateral microcirculation of cirrhotic rats. Thalidomide seems to be a promising agent that might bring about beneficial changes to the disarrangements of peripheral, hepatic, splanchnic and collateral systems in cirrhosis.

Dataset Information

Endogenous hormone 2-methoxyestradiol suppresses venous hypertension-induced angiogenesis through up- and down-regulating p53 and id-1.

Publications

Endogenous hormone 2-methoxyestradiol suppresses venous hypertension-induced angiogenesis through up- and down-regulating p53 and id-1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure