Next Article in Journal
Temporal Trends of Severe Hypoglycemia and Subsequent Mortality in Patients with Advanced Diabetic Kidney Diseases Transitioning to Dialysis
Previous Article in Journal
Role of Mucosal Protrusion Angle in Discriminating between True and False Masses of the Small Bowel on Video Capsule Endoscopy
Article

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

1
Liver Unit, Austin Health, Melbourne 3084, Australia
2
Department of Medicine, Austin Health, University of Melbourne, Melbourne 3084, Australia
3
Department of Internal Medicine I, University of Bonn, 53113 Bonn, Germany
4
Department of Internal Medicine I, Goethe University Clinic Frankfurt, 60323 Frankfurt, Germany
5
Victorian Infectious Disease Reference Laboratory, the Peter Doherty Institute for Infection and Immunity, Melbourne Health, Melbourne 3000, Australia
6
Institute of Cellular Medicine, Fibrosis Research Group, Newcastle upon Tyne NE2 4HH, UK
7
Department of Radiology, University of Bonn, 53113 Bonn, Germany
8
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain
9
European Foundation for the Study of Chronic Liver Failure, 08021 Barcelona, Spain
10
Department of Gastroenterology and Hepatology, Odense University Hospital, 5000 Odense, Denmark
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(4), 419; https://doi.org/10.3390/jcm8040419
Received: 27 February 2019 / Revised: 16 March 2019 / Accepted: 21 March 2019 / Published: 27 March 2019
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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. View Full-Text
Keywords: cirrhosis; portal hypertension; renin-angiotensin system cirrhosis; portal hypertension; renin-angiotensin system
Show Figures

Figure 1

MDPI and ACS Style

Casey, S.; Schierwagen, R.; Mak, K.Y.; Klein, S.; Uschner, F.; Jansen, C.; Praktiknjo, M.; Meyer, C.; Thomas, D.; Herath, C.; Jones, R.; Trebicka, J.; Angus, P. Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation. J. Clin. Med. 2019, 8, 419. https://doi.org/10.3390/jcm8040419

AMA Style

Casey S, Schierwagen R, Mak KY, Klein S, Uschner F, Jansen C, Praktiknjo M, Meyer C, Thomas D, Herath C, Jones R, Trebicka J, Angus P. Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation. Journal of Clinical Medicine. 2019; 8(4):419. https://doi.org/10.3390/jcm8040419

Chicago/Turabian Style

Casey, Stephen, Robert Schierwagen, Kai Y. Mak, Sabine Klein, Frank Uschner, Christian Jansen, Michael Praktiknjo, Carsten Meyer, Daniel Thomas, Chandana Herath, Robert Jones, Jonel Trebicka, and Peter Angus. 2019. "Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation" Journal of Clinical Medicine 8, no. 4: 419. https://doi.org/10.3390/jcm8040419

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop