Overexpression of angiopoietin‐2 in rats and patients with liver fibrosis. Therapeutic consequences of its inhibition. (11th March 2014)

• Record Type: Journal Article
• Authors: Pauta, Montse; Ribera, Jordi; Melgar‐Lesmes, Pedro; Casals, Gregori; Rodríguez‐Vita, Juan; Reichenbach, Vedrana; Fernandez‐Varo, Guillermo; Morales‐Romero, Blai; Bataller, Ramon; Michelena, Javier; Altamirano, Jose; Jiménez, Wladimiro; Morales‐Ruiz, Manuel
• Is Part Of: Liver international. Volume 35:Number 4(2015:Apr.)
• Page Start: 1383
• Page End: 1392
• Publication Date: 2014-03-11
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12505
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12505-abs-0001"> <title>Abstract</title> <sec id="liv12505-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Studies in experimental models of cirrhosis showed that anti‐angiogenic treatments may be effective for the treatment of liver fibrosis. In this context, angiopoietins are potential therapeutic targets as they are involved in the maintenance and stabilization of newly formed blood vessels. In addition, angiopoietin‐2 is expressed in fibrotic livers and its inhibition in tumours results in vessel stability. Therefore, our study was aimed to assess the therapeutic utility of inhibiting angiopoietin‐2.</p> </sec> <sec id="liv12505-sec-0002" sec-type="section"> <title>Methods</title> <p>Circulating levels of angiopoietin‐1 and angiopoietin‐2 were quantified by ELISA in CCl<sub>4</sub>‐treated rats and in patients with cirrhosis. <italic>In vivo</italic> blockade of angiopoietin‐2 in rats with liver fibrosis was performed with a chemically programmed antibody, CVX‐060.</p> </sec> <sec id="liv12505-sec-0003" sec-type="section"> <title>Results</title> <p>High levels of angiopoietin‐2 were found in the systemic and suprahepatic circulation of cirrhotic patients and the ratio angiopoietin‐1/angiopoietin‐2 inversely correlated with prognostic models for alcoholic liver disease. Chronic treatment of CCl<sub>4</sub>‐treated rats with CVX‐060 was associated with a significant decrease in inflammatory infiltrate, normalization of the hepatic microvasculature and reduction in VCAM‐1 vascular expression. The anti‐angiopoietin‐2 treatment was also associated with less liver fibrosis and with lower levels of circulating transaminases. CVX‐060 treatment was not associated with either vascular pruning in healthy tissue or compensatory overexpression of VEGF.</p> </sec> <sec id="liv12505-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Inhibition of angiopoietin‐2 is an effective and safe treatment for liver fibrosis in CCl<sub>4</sub>‐treated rats, acting mainly through the induction of vessel normalization and the attenuation of hepatic inflammatory infiltrate. Therefore, inhibition of angiopoietin‐2 offers a therapeutic alternative for liver fibrosis.</p> </sec> </abstract>