Cited by 127Apelin-related biomedical researchLiver Disease and TransplantationLiver physiology and pathology

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The hepatic apelin system: A new therapeutic target for liver disease†

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Principe, Alessandro, Melgar‐Lesmes, Pedro, Fernández‐Varo, Guillermo, del Arbol, Luis Ruiz, Ros, Josefa, Morales‐Ruiz, Manuel, Bernardi, Mauro, Arroyo, Vicente, Jiménez, Wladimiro·2008·Hepatology

DOI 10.1002/hep.22467

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Abstract

UNLABELLED: Apelin is a peptide that plays an important role in heart physiology and pathophysiology, inflammation, and angiogenesis. We evaluated whether the endogenous apelin system is involved in the pathogenesis of the hepatic remodeling and cardiovascular and renal complications occurring in advanced liver disease. The circulating levels of apelin, the messenger RNA (mRNA) and protein expression of apelin and apelin receptor, the immunohistological detection of apelin and apelin receptor, and the effects induced by the chronic administration of an apelin receptor antagonist on fibrosis and vessel density were evaluated in rats with cirrhosis and ascites and in control rats. The serum levels of apelin in patients with cirrhosis were also measured. Apelin levels were higher in rats with cirrhosis than in controls. Apelin mRNA showed a four-fold rise only in hepatic tissue, but not in the lung, heart, or kidney of rats with cirrhosis. These animals also showed hepatic apelin receptor mRNA levels 300 times higher than controls. Apelin was highly expressed by stellate cells, whereas apelin receptor was overexpressed in the hepatic parenchyma of animals with cirrhosis. Rats with cirrhosis treated with the apelin receptor antagonist showed diminished hepatic fibrosis and vessel density, improved cardiovascular performance, and renal function and lost ascites. Human patients also showed a marked increase in apelin levels. CONCLUSION: The selective hepatic activation of the apelin system, together with the drop in fibrosis and neoangiogenesis and the improvement in cardiovascular and excretory function resulting from apelin receptor blockade, points to the hepatic apelin system as a novel therapeutic target in liver disease.

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Authors: Principe, A., Melgar‐Lesmes, P., Fernández‐Varo, G., del Arbol, L. R., Ros, J., Morales‐Ruiz, M., Bernardi, M., Arroyo, V., & Jiménez, W.
Affiliations: Hospital Clínic de Barcelona (ES)
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
Corresponding author: Jiménez, Wladimiro
ORCID: Melgar‐Lesmes, Pedro
Fernández‐Varo, Guillermo
Morales‐Ruiz, Manuel
Bernardi, Mauro
Arroyo, Vicente
Jiménez, Wladimiro
Venue: Hepatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-10
Volume: 48
Issue: 4
Pages: 1193-1201
ISSN: 0270-9139 (ISSN-L)
DOI: 10.1002/hep.22467
OpenAlex: W1978999795
Cited by: 127
References: 32
Citations by year: 2026: 2 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 7 · 2020: 11 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 17 · 2014: 10 · 2013: 7 · 2012: 9
FWCI: 6.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 2526 d)
Locations: Hepatology (publishedVersion)
PubMed (publishedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Apelin-related biomedical research
Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: apelin, apelin receptor, liver cirrhosis, liver fibrosis, ascites, hepatic stellate cells, neoangiogenesis, cardiovascular complications, renal function, advanced liver disease, therapeutic target
MeSH terms: Apelin, Adult, Animals, Blood Pressure, Carbon Tetrachloride, Carrier Proteins, Disease Models, Animal, Female, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Renin-Angiotensin System, RNA, Messenger, Sympathetic Nervous System, Vascular Resistance, Case-Control Studies, Rats, Wistar, Intercellular Signaling Peptides and Proteins, Rats

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The hepatic apelin system: A new therapeutic target for liver disease†

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