The systemic and hepatic alternative renin–angiotensin system is activated in liver cirrhosis, linked to endothelial dysfunction and inflammation

Figures

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  Figure 1. Components of the classical and alternative renin–angiotensin system (RAS) in patients with compensated (cACLD, n = 13) and decompensated cirrhosis (dACLD, n = 12). (a) Depiction of the RAS fingerprint in patients with cACLD and dACLD. Comparison of quantitative levels of (b) classical RAS components (Ang I and Ang II) and (c) alternative RAS components (Ang 1–7, Ang 1–5) between patients with cACLD and dACLD. For RAS fingerprint analysis, the size of the spheres and numbers beside them represent the median absolute concentrations of angiotensins (pmol/L) analyzed by mass spectrometry. Ang angiotensin, ACE angiotensin converting enzyme, AP aminopeptidase, cACLD compensated advanced chronic liver disease, dACLD decompensated advanced chronic liver disease, DAP dipeptidyl aminopeptidase, NEP neprilysin, RAS renin–angiotensin system.

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  Figure 2. Correlations between components of the classical and alternative RAS (PRA-S, Ang I, Ang II and Ang 1–7) and parameters of liver disease severity (MELD), severity of portal hypertension (HVPG), liver stiffness (LSM), endothelial dysfunction (vWF) and inflammation (IL-6). Correlations were assessed using Spearman’s Rho. ∗ denotes p values < 0.05, whereas ∗∗ indicates p values < 0.001. Ang angiotensin, HVPG hepatic venous pressure gradient, IL-6 interleukin-6, LSM liver stiffness measurement, MELD model for end-stage liver disease, RAS renin–angiotensin system, PRA-S plasma renin activity surrogate, vWF von Willebrand factor antigen.

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  Figure 3. Tissue activity of components of the (a,b) classical (ACE, chymase) and (c,d) alternative RAS (neprilysin [NEP], ACE2) in 5 patients with compensated (cACLD; n = 3) and decompensated advanced chronic liver disease (dACLD; n = 2). ACE angiotensin converting enzyme, cACLD compensated advanced chronic liver disease, dACLD decompensated advanced chronic liver disease, NEP neprilysin, RAS renin–angiotensin system.