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Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation

Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension....

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Autores principales: Casey, Stephen, Schierwagen, Robert, Mak, Kai Yan, Klein, Sabine, Uschner, Frank, Jansen, Christian, Praktiknjo, Michael, Meyer, Carsten, Thomas, Daniel, Herath, Chandana, Jones, Robert, Trebicka, Jonel, Angus, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518205/
https://www.ncbi.nlm.nih.gov/pubmed/30934723
http://dx.doi.org/10.3390/jcm8040419
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author Casey, Stephen
Schierwagen, Robert
Mak, Kai Yan
Klein, Sabine
Uschner, Frank
Jansen, Christian
Praktiknjo, Michael
Meyer, Carsten
Thomas, Daniel
Herath, Chandana
Jones, Robert
Trebicka, Jonel
Angus, Peter
author_facet Casey, Stephen
Schierwagen, Robert
Mak, Kai Yan
Klein, Sabine
Uschner, Frank
Jansen, Christian
Praktiknjo, Michael
Meyer, Carsten
Thomas, Daniel
Herath, Chandana
Jones, Robert
Trebicka, Jonel
Angus, Peter
author_sort Casey, Stephen
collection PubMed
description Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.
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spelling pubmed-65182052019-05-31 Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation Casey, Stephen Schierwagen, Robert Mak, Kai Yan Klein, Sabine Uschner, Frank Jansen, Christian Praktiknjo, Michael Meyer, Carsten Thomas, Daniel Herath, Chandana Jones, Robert Trebicka, Jonel Angus, Peter J Clin Med Article Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis. MDPI 2019-03-27 /pmc/articles/PMC6518205/ /pubmed/30934723 http://dx.doi.org/10.3390/jcm8040419 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Casey, Stephen
Schierwagen, Robert
Mak, Kai Yan
Klein, Sabine
Uschner, Frank
Jansen, Christian
Praktiknjo, Michael
Meyer, Carsten
Thomas, Daniel
Herath, Chandana
Jones, Robert
Trebicka, Jonel
Angus, Peter
Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation
title Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation
title_full Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation
title_fullStr Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation
title_full_unstemmed Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation
title_short Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation
title_sort activation of the alternate renin-angiotensin system correlates with the clinical status in human cirrhosis and corrects post liver transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518205/
https://www.ncbi.nlm.nih.gov/pubmed/30934723
http://dx.doi.org/10.3390/jcm8040419
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