Role of placental growth factor in mesenteric neoangiogenesis in a mouse model of portal hypertension
Steenkiste, Van, Christophe
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Veterinary Sciences
Gastroenterology. - Baltimore, Md
, p. 2112-2124
Background & Aims Portal hypertension is responsible for the major complications associated with cirrhosis. Angiogenesis has been associated with the pathophysiology of portal hypertension. We investigated the role of placental growth factor (PlGF) and tested the effects of monoclonal antibodies against PlGF (αPlGF) in a mouse model of portal hypertension. Methods Using a mouse model of prehepatic portal hypertension, we measured PlGF levels in the mesenteric tissue at different time points. We used knockout mice and αPlGF to determine the role of PlGF in the splanchnic hyperdynamic system and portosystemic collateral formation, examining its effects before and after portal hypertension was induced. Results PlGF was significantly up-regulated in the mesenteric tissue of mice with portal hypertension. Compared with wild-type animals, the vascular density in the mesentery was reduced in PlGF knockout hypertensive mice, preventing collateral formation and attenuation of mesenteric artery flow without affecting portal pressure. In the prevention study, αPlGF showed similar findings as in the knockout study. In mice with portal hypertension, administration of αPlGF resulted in a 32% decrease in portal pressure, compared with mice given immunoglobulin G1 (control). Conclusions Pathologic angiogenesis in the mesenteric tissues of mice with portal hypertension is mediated by PlGF. Blocking PlGF could be an effective strategy for reducing collateral formation and lowering portal pressure; further research into the effects in cirrhosis is warranted.