To investigate the possible role of the Angiopoietins in vessel remodelling, we overexpressed one of the angiopoietins, Angiopoietin-1 (Ang1), in the hepatocytes of mice by means of the conditional binary transgenic system. Animals were examined by Doppler ultrasound, and dissected livers were analyzed by immunohistochemical staining. Double transgenic mice presented with enlarged spleens and kidneys, enlarged, disorganized blood vessels located near the surface of the liver, sprouting, dilation, and disorganization of liver lymphatics, and turbulent flow in about 1/4 of the blood vessels sampled. Most of these characteristics completely resolved within 12 weeks of turning off the expression of the Ang1 transgene, illustrating a dependence on the continual presence of Ang1 for maintenance of the vascular phenotype. Conditional Angiopoietin-1 overexpression in the liver of mice leads to a phenotype highly reminiscent of portal hypertension illustrating that Ang1 can drive both vascular and lymphatic vessel remodelling and may play a role in portal hypertension. (c) 2006 Elsevier Inc. All rights reserved.