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

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

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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Crossref · 10.1002/hep.22467

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Metadata

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
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
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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