ArticlePloS one2015
Hemodynamic Effects of the Non-Peptidic Angiotensin-(1-7) Agonist AVE0991 in Liver Cirrhosis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 34 citations in OpenAlex.
- From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension.Metabolites · 2025Review
- The Renin-Angiotensin System in Liver Disease.International journal of molecular sciences · 2024Review
- Emerging Therapeutic Targets for Portal Hypertension.Current hepatology reports · 2023Review
- Mas-related G protein-coupled receptor type D antagonism improves portal hypertension in cirrhotic rats.Hepatology communications · 2022Article
- Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy.JHEP reports : innovation in hepatology · 2021Review
- Update on New Aspects of the Renin-Angiotensin System in Hepatic Fibrosis and Portal Hypertension: Implications for Novel Therapeutic Options.Journal of clinical medicine · 2021Review
- Liver Fibrosis-From Mechanisms of Injury to Modulation of Disease.Frontiers in medicine · 2021Review
- Angiotensin-(1-7): Translational Avenues in Cardiovascular Control.American journal of hypertension · 2019Review
- TGR(mREN2)27 rats develop non-alcoholic fatty liver disease-associated portal hypertension responsive to modulations of Janus-kinase 2 and Mas receptor.Scientific reports · 2019Article
- Rho-kinase inhibitor coupled to peptide-modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats.Scientific reports · 2019Article
- Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon.Hepatology international · 2018Review
- Advances in therapeutic options for portal hypertension.Therapeutic advances in gastroenterology · 2018Review
- Managing portal hypertension in patients with liver cirrhosis.F1000Research · 2018Review
- Anti-atherosclerotic effect of the angiotensin 1-7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis.British journal of pharmacology · 2017Article
- Novel treatment options for portal hypertension.Gastroenterology report · 2017Article
- Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22.British journal of pharmacology · 2017Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsAlthough in cirrhosis with portal hypertension levels of the vasoconstrictor angiotensin II are increased, this is accompanied by increased production of angiotensin (Ang)-(1-7), the endogenous ligand of the Mas receptor (MasR), which blunts hepatic fibrosis and decreases hepatic vascular resistance. Therefore, we investigated the effects of the non-peptidic Ang-(1-7) agonist, AVE0991, in experimental cirrhosis.
methodsCirrhosis was induced by bile duct ligation (BDL) or carbon tetrachloride (CCl4) intoxication. The coloured microsphere technique assessed portal and systemic hemodynamic effects of AVE0991 in vivo. Hepatic expression of eNOS, p-eNOS, iNOS, JAK2, ROCK and p-Moesin were analyzed by western blots. Activities of ACE and ACE2 were investigated fluorometrically. Moreover, fibrosis was assessed in BDL rats receiving AVE0991.
resultsIn vivo, AVE0991 decreased portal pressure (PP) in both rat models of cirrhosis. Importantly, systemic effects were not observed. The hepatic effects of AVE0991 were based on upregulation of vasodilating pathways involving p-eNOS and iNOS, as well as by downregulation of the vasoconstrictive pathways (ROCK, p-Moesin). Short-term treatment with AVE0991 decreased the activity of ACE2, long-term treatment did not affect hepatic fibrosis in BDL rats.
conclusionsThe non-peptidic agonist of Ang-(1-7), AVE0991, decreases portal pressure without influencing systemic pressure. Thus, although it does not inhibit fibrosis, AVE0991 may represent a promising new therapeutic strategy for lowering portal pressure.
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