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J Hepatol. 2005 Jul;43(1):85-91. Epub 2005 Apr 12.

Ascites from cirrhotic patients induces angiogenesis through the phosphoinositide 3-kinase/Akt signaling pathway.

Author information

1
Hormonal Laboratory, Hospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Villarroel 170 Barcelona 08036, Spain. mmoralesruiz@ub.edu

Abstract

BACKGROUND/AIMS:

Ascites in patients with cirrhosis is associated with worsening of systemic hemodynamics. Thus, the aim of this study was to investigate the biological activity of ascites on endothelial cells.

METHODS:

Human umbilical vein endothelial cells (HUVECs) were used to investigate the angiogenic activity of ascites obtained from cirrhotic patients.

RESULTS:

Ascites-induced Akt activation, cell migration and tube formation in HUVECs. The pretreatment of HUVECs with the phosphatidylinositide 3-kinase (PI3-kinase) inhibitor LY294002, resulted in a decrease in chemotaxis and cell tube formation induced by ascites. Moreover, the inhibition of Akt activity in HUVECs by transduction of an inactive phosphorylation Akt mutant (AA-Akt), blocked tube formation. These angiogenic effects of ascites were also operative in vivo showing a PI3-kinase activation dependence in the angiogenesis induced by ascites. In addition, the preincubation of ascites with anti-fibronectin antibody led to a significant decrease in HUVECs migration, cell tube formation and in vivo angiogenesis.

CONCLUSIONS:

These results confirm the novel concept that ascites is a bioactive fluid which can modify vascular properties through the activation of the PI3-kinase/Akt pathway in endothelial cells. Furthermore, our results demonstrated that this ascites-induced mechanism is mediated, at least in part, by fibronectin.

PMID:
15890430
DOI:
10.1016/j.jhep.2005.01.035
[Indexed for MEDLINE]

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