Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, HYPERDYNAMIC SPLANCHNIC CIRCULATION, PERITONEAL-MACROPHAGES, CIRRHOTIC-PATIENTS, FACTOR RECEPTOR-1, BLOOD-FLOW, ANGIOGENESIS, PRESSURE, VESSELS, RATS, MICE, Angiogenic Proteins, Animals, Antibodies, Monoclonal, Antihypertensive Agents, Collateral Circulation, Disease Models, Animal, Hypertension, Portal, Kinetics, Male, Mesentery, Mice, Mice, Knockout, Microcirculation, Neovascularization, Pathologic, Placenta Growth Factor, Portal Pressure, Pregnancy Proteins, Signal Transduction, Splanchnic Circulation, Up-Regulation, 1103 Clinical Sciences, 1109 Neurosciences, 1114 Paediatrics and Reproductive Medicine, 3202 Clinical sciences, 3210 Nutrition and dietetics

Abstract:

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 (alphaPlGF) in a mouse model of portal hypertension. METHODS:: Using a mouse model of pre-hepatic portal hypertension, we measured PlGF levels in the mesenteric tissue at different timepoints. We used knockout mice and alphaPlGF to determine the role of PlGF in the splanchnic hyperdynamic system and porto-systemic collateral formation, examining its effects before and after portal hypertension was induced. RESULTS:: PlGF was significantly upregulated 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, alphaPlGF showed similar findings as in the knockout study. Administration of alphaPlGF resulted in a 32% decrease in portal pressure, compared with mice given immunoglobulin G(1) (control), in mice with portal hypertension. CONCLUSION:: Pathological 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.