Why the study?
Animal studies showed the alternate renin-angiotensin system is upregulated in cirrhosis, but its expression and relationship to clinical status in human liver disease required evaluation.
Does liver transplantation or TIPS correct the upregulated alternate renin-angiotensin system in patients with cirrhosis?
Does liver transplantation or TIPS correct the upregulated alternate renin-angiotensin system in patients with cirrhosis?
The alternate renin-angiotensin system is markedly upregulated in human cirrhosis, correlates with disease severity and hyperdynamic circulation, and normalizes after liver transplantation.
Normalization of alternate RAS post-transplant supports its link to cirrhosis severity and hyperdynamic circulation; leaves open therapeutic implications.
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.
No takes yet. Share an insight, caveat, or question.
Casey et al. (2019) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: