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

along with a 30 opercent decrease in superior mesenteric artery blood flow and a 63 percent increase in superior mesenteric artery resistance. This was a significant reversal of the hemodynamic changes provoked by portal hypertension in rats, the authors report.

They found that the magnitude of the effects of the combination treatment was superior to the addition of the effects of either drug alone, suggesting that the two worked together to mediate the maintenance of the vascular and circulatory abnormalities observed in rats with portal hypertension.

This is the first study to show that portal hypertension development is associated with a progressive overexpression of PDGF as well as VEGF. It also revealed that anti-angiogenic therapy could not merely prevent, but also revert, abnormalities associated with portal hypertension which would be a very helpful for treating patients with portal hypertension, because they are typically only diagnosed when their condition causes clinical problems. Furthermore, both drugs tested in this study have already been broadly used to treat human malignancies.

Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchic neovascularization and portosystemic collaterization is regulated by VEGF and PDGF in portal hypertensive rats, the authors conclude. An extended anti-angiogenic strategy (i.e. targeting VEGF/endothelium and PDGF/pericytes) may represent a novel approach in the treatment of portal hypertension.


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Contact: Amy Molnar
amolnar@wiley.com
John Wiley & Sons, Inc.
Source:Eurekalert

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