Blood cyclic guanosine monophosphate levels as potential marker of portal hypertension in patients with liver cirrhosis

2021 ◽  
Author(s):  
L Sturm ◽  
L Roth ◽  
D Bettinger ◽  
K Zoldan ◽  
T Boettler ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Potential Marker

scholarly journals Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension

2020 ◽  
Vol 21 (17) ◽  
pp. 6223 ◽  
Author(s):  
Wolfgang Kreisel ◽  
Denise Schaffner ◽  
Adhara Lazaro ◽  
Jonel Trebicka ◽  
Irmgard Merfort ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Current Knowledge ◽  
Health Care Systems ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Regulatory Enzymes ◽  
Care Systems ◽  
Human Liver Cirrhosis

Liver cirrhosis is a frequent condition with high impact on patients’ life expectancy and health care systems. Cirrhotic portal hypertension (PH) gradually develops with deteriorating liver function and can lead to life-threatening complications. Other than an increase in intrahepatic flow resistance due to morphological remodeling of the organ, a functional dysregulation of the sinusoids, the smallest functional units of liver vasculature, plays a pivotal role. Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Recent data showed characteristic alterations in the expression of these regulatory enzymes or metabolite levels in liver cirrhosis. Additionally, a disturbed zonation of the components of this pathway along the sinusoids was detected. This review describes current knowledge of the pathophysiology of PH with focus on the enzymes regulating cGMP availability, i.e., sGC and PDE-5. The results have primarily been obtained in animal models of liver cirrhosis. However, clinical and histochemical data suggest that the new biochemical model we propose can be applied to human liver cirrhosis. The role of PDE-5 as potential target for medical therapy of PH is discussed.

scholarly journals Plasma Cyclic Guanosine Monophosphate Is a Promising Biomarker of Clinically Significant Portal Hypertension in Patients With Liver Cirrhosis

2022 ◽  
Vol 8 ◽  
Author(s):  
Lukas Sturm ◽  
Dominik Bettinger ◽  
Lisa Roth ◽  
Katharina Zoldan ◽  
Laura Stolz ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Esophageal Varices ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Healthy Controls ◽  
Screening Endoscopy ◽  
Portal Decompression ◽  
Potential Biomarker ◽  
Cirrhotic Patients ◽  
Clinically Significant

Introduction: Despite intensive research, reliable blood-derived parameters to detect clinically significant portal hypertension (CSPH) in patients with cirrhosis are lacking. As altered homeostasis of cyclic guanosine monophosphate (cGMP), the central mediator of vasodilatation, is an essential factor in the pathogenesis of portal hypertension, the aim of our study was to evaluate plasma cGMP as potential biomarker of cirrhotic portal hypertension.Methods: Plasma cGMP was analyzed in cirrhotic patients with CSPH (ascites, n = 39; esophageal varices, n = 31), cirrhotic patients without CSPH (n = 21), patients with chronic liver disease without cirrhosis (n = 11) and healthy controls (n = 8). cGMP was evaluated as predictor of CSPH using logistic regression models. Further, the effect of transjugular intrahepatic portosystemic shunt (TIPS) placement on plasma cGMP was investigated in a subgroup of cirrhotic patients (n = 13).Results: Plasma cGMP was significantly elevated in cirrhotic patients with CSPH compared to cirrhotic patients without CSPH [78.1 (67.6–89.2) pmol/ml vs. 39.1 (35.0–45.3) pmol/l, p < 0.001]. Of note, this effect was consistent in the subgroup of patients with esophageal varices detected at screening endoscopy who had no prior manifestations of portal hypertension (p < 0.001). Cirrhotic patients without CSPH displayed no significant elevation of plasma cGMP compared to patients without cirrhosis (p = 0.347) and healthy controls (p = 0.200). Regression analyses confirmed that cGMP was an independent predictor of CSPH (OR 1.042, 95% CI 1.008–1.078, p = 0.016). Interestingly, portal decompression by TIPS implantation did not lead to normalization of plasma cGMP levels (p = 0.101).Conclusions: Plasma cGMP is a promising biomarker of CSPH in patients with cirrhosis, especially with respect to screening for esophageal varices. The lacking normalization of plasma cGMP after portal decompression suggests that elevated plasma cGMP in cirrhotic portal hypertension is mainly a correlate of systemic and splanchnic vasodilatation, as these alterations have been shown to persist after TIPS implantation.

scholarly journals Cyclic GMP in Liver Cirrhosis—Role in Pathophysiology of Portal Hypertension and Therapeutic Implications

2021 ◽  
Vol 22 (19) ◽  
pp. 10372
Author(s):  
Wolfgang Kreisel ◽  
Adhara Lazaro ◽  
Jonel Trebicka ◽  
Markus Grosse Perdekamp ◽  
Annette Schmitt-Graeff ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Therapeutic Potential ◽  
Portal Pressure ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Venous Blood Flow ◽  
Cgmp Signal

The NO-cGMP signal transduction pathway plays a crucial role in tone regulation in hepatic sinusoids and peripheral blood vessels. In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). This results in constriction of hepatic sinusoids, contributing about 30% of portal pressure. In contrast, in peripheral arteries, dilation prevails with excess cGMP due to low PDE-5. Both effects eventually lead to circulatory dysfunction in progressed liver cirrhosis. The conventional view of portal hypertension (PH) pathophysiology has been described using the “NO-paradox”, referring to reduced NO availability inside the liver and elevated NO production in the peripheral systemic circulation. However, recent data suggest that an altered availability of cGMP could better elucidate the contrasting findings of intrahepatic vasoconstriction and peripheral systemic vasodilation than mere focus on NO availability. Preclinical and clinical data have demonstrated that targeting the NO-cGMP pathway in liver cirrhosis using PDE-5 inhibitors or sGC stimulators/activators decreases intrahepatic resistance through dilation of sinusoids, lowering portal pressure, and increasing portal venous blood flow. These results suggest further clinical applications in liver cirrhosis. Targeting the NO-cGMP system plays a role in possible reversal of liver fibrosis or cirrhosis. PDE-5 inhibitors may have therapeutic potential for hepatic encephalopathy. Serum/plasma levels of cGMP can be used as a non-invasive marker of clinically significant portal hypertension. This manuscript reviews new data about the role of the NO-cGMP signal transduction system in pathophysiology of cirrhotic portal hypertension and provides perspective for further studies.

Small intestinal motillity disturbances and bacterial overgrowth in patients with liver cirrhosis is associated with portal hypertension

2001 ◽  
Vol 120 (5) ◽  
pp. A224-A224
Author(s):  
A GUNNARSDOTTIR ◽  
E BJOMSSON ◽  
G RINGSTROM ◽  
M SIMREN ◽  
P STOTZER ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Bacterial Overgrowth ◽  
Small Intestinal

An unusual presentation of epigastric pain due to thrombophlebitis of a recanalised umbilical vein – case report

2019 ◽  
Vol 98 (8) ◽  
pp. 326-327 ◽  
Keyword(s):  
Liver Cirrhosis ◽  
Abdominal Pain ◽  
Case Report ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Epigastric Pain ◽  
Umbilical Vein ◽  
History Of ◽  
Clinically Significant ◽  
Inflammatory Changes

Introduction: The umbilical vein can become recanalised due to portal hypertension in patients with liver cirrhosis but the condition is rarely clinically significant. Although bleeding from this enlarged vein is a known complication, the finding of thrombophlebitis has not been previously described. Case report: We report the case of a 62-year-old male with a history of liver cirrhosis due to alcoholic liver disease presenting to hospital with epigastric pain. A CT scan of the patient’s abdomen revealed a thrombus with surrounding inflammatory changes in a recanalised umbilical vein. The patient was managed conservatively and was discharged home the following day. Conclusion: Thrombophlebitis of a recanalised umbilical vein is a rare cause of abdominal pain in patients with liver cirrhosis.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

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