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

Rapamycin prevents mesenteric neo‐angiogenesis and reduces splanchnic blood flow in portal hypertensive mice

“…The findings in the present study may indicate an involvement of the PI3K/Akt/mTOR signalling pathway in the increased mesenteric angiogenesis in portal hypertensive mice and can lead to new targets to block pathological angiogenesis. Previously, phosphorylation of Akt was shown to be enhanced significantly in mesenteric arteries of portal hypertensive rats, and played a role in the upregulation of eNOS activity 27,28 . TNF‐alpha has also been shown to be indirectly a contributor to the hyperdynamic circulation likely through activation of NO synthase.…”

“…Previously, phosphorylation of Akt was shown to be enhanced significantly in mesenteric arteries of portal hypertensive rats, and played a role in the upregulation of eNOS activity. 27,28 TNF-alpha has also been shown to be indirectly a contributor to the hyperdynamic circulation likely through activation of NO synthase. Previously published data shows that elevated TNF-alpha in PHT gastric mucosa likely activates the PI3kinase-Akt signalling pathway and subsequently phosphorylation of eNOS at serine 1177 leading to its activation.…”

Antiangiogenic treatment with Sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats

“…There is significant evidence suggesting that the increase in portal blood flow is due not only to splanchnic vasodilation but also to an enlargement of the splanchnic vascular tree caused by angiogenesis. 7,28,29 Therefore, we anticipated that the significant inhibition of angiogenesis promoted by SU11248 in this anatomic region might translate into a significant decrease in portal blood flow.…”

Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats

“…Because of this relatively simple composition the presence of ascites was classically considered to have little or no influence on the homeostasis of the peritoneal vasculature. Nevertheless, this has recently been challenged by several studies demonstrating that this liquid may possess vasodilator, proinflammatory and proangiogenic properties 2 – 7. However, whereas it is well documented that ascites in cirrhosis may behave as a bioactive fluid, the source of this liquid and the molecular gates regulating fluid extravasation in cirrhosis are less clear.…”