TY  - JOUR
A1  - Casey, Stephen
A1  - Schierwagen, Robert
A1  - Mak, Kai Yan
A1  - Klein, Sabine
A1  - Uschner, Frank Erhard
A1  - Jansen, Christian
A1  - Praktiknjo, Michael
A1  - Meyer, Carsten
A1  - Thomas, Daniel
A1  - Herath, Chandana
A1  - Jones, Robert
A1  - Trebicka, Jonel
A1  - Angus, Peter
T1  - Activation of the alternate renin-angiotensin system correlates with the clinical status in human cirrhosis and corrects post liver transplantation
T2  - Journal of Clinical Medicine
N2  - 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.
KW  - cirrhosis
KW  - portal hypertension
KW  - renin-angiotensin system
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51508
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-515087
SN  - 2077-0383
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
VL  - 8
IS  - 4, Art. 419
SP  - 1
EP  - 13
PB  - MDPI
CY  - Basel
ER  -