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Combination therapy reverses effects of portal hypertension in rats
Date:10/1/2007

A combined treatment with rapamycin and Gleevec might reverse the effects of portal hypertension in patients with chronic liver disease, according to the results of a new study on rats. The study is in the October issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (http://www.interscience.wiley.com/journal/hepatology).

Portal hypertension is a serious complication of chronic liver disease, and a leading cause of liver transplantation and mortality. It develops when a blockage in the blood flow through the liver causes the body to develop new blood vessels to develop (through a process called angiogenesis) across the esophagus and stomach. These new vessels drain into the portal vein, worsening the portal blood pressure and contributing to the formation of life-threatening complications like esophageal varices. Prior studies have suggested that anti-angiogenic treatment might help prevent the progression of the portal hypertension syndrome.

Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) are crucial to angiogenesis, so researchers, led by Mercedes Fernandez of the IDIBAPS in Barcelona, examined the effects of VEGF and PDGF inhibitory drugs on rats with established portal hypertension, to best mimic the typical human patient. They treated portal vein-ligated rats with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor) or both simultaneously, and determined the effects on hyperdynamic splanchnic circulation and portosystemic collateralization.

In rats whose portal hypertension was fully developed, the combined therapy significantly reduced splanchnic neovascularization and pericyte coverage of neovessels. The rats experienced a 40 percent decrease in portal pressure,
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Contact: Amy Molnar
amolnar@wiley.com
John Wiley & Sons, Inc.
Source:Eurekalert

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