Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis

Queck, Alexander; Thomas, Dominique; Jansen, Christian; Schreiber, Yannick; Rüschenbaum, Sabrina; Praktiknjo, Michael; Schwarzkopf, K; Mücke, Marcus M.; Schierwagen, Robert; Uschner, Frank Erhard; Meyer, Carsten H.; Clària, Joan; Zeuzem, Stefan; Geißlinger, Gerd; Trebicka, Jonel; Lange, Christian

doi:10.1371/journal.pone.0222840

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…The same authors found an association between elevated levels of thromboxane B2 in the portal circulation and portal hepatic venous pressure gradient. They concluded that thromboxane B2 is possibly associated with prothrombotic potential [63]. In the paper by Eyraud et al [52], soluble P selectin decreased after liver transplantation, suggesting a higher soluble P selectin/platelet count ratio in cirrhotic patients before transplantation.…”

Section: Soluble Release Markersmentioning

confidence: 97%

Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?

Dievoet

Eeckhoudt

Stéphenne

2020

IJMS

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Changes in primary hemostasis have been described in patients with chronic liver disease (CLD) and cirrhosis and are still subject to ongoing debate. Thrombocytopenia is common and multifactorial. Numerous studies also reported platelet dysfunction. In spite of these changes, primary hemostasis seems to be balanced. Patients with CLD and cirrhosis can suffer from both hemorrhagic and thrombotic complications. Variceal bleeding is the major hemorrhagic complication and is mainly determined by high portal pressure. Non portal hypertension-related bleeding due to hemostatic failure is uncommon. Thrombocytopenia can complicate management of invasive procedures in CLD patients. Recently, oral thrombopoietin agonists have been approved to raise platelets before invasive procedures. In this review we aim to bundle literature, published over the past decade, discussing primary hemostasis in CLD and cirrhosis including (1) platelet count and the role of thrombopoietin (TPO) agonists, (2) platelet function tests and markers of platelet activation, (3) von Willebrand factor and (4) global hemostasis tests.

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Section: Soluble Release Markersmentioning

confidence: 97%

Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?

Dievoet

Eeckhoudt

Stéphenne

2020

IJMS

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“…COXs generate prostanoids, and several have contractile effects on smooth muscle 50 . Prostaglandin E 2 is found in portal vein 55 . We tested the effect of prostaglandin E 2 and observed concentration‐dependent contraction (Figure 4D).…”

Section: Resultsmentioning

confidence: 95%

“… 50 Prostaglandin E 2 is found in portal vein. 55 We tested the effect of prostaglandin E 2 and observed concentration‐dependent contraction (Figure 4D ). The EC 50 for the prostaglandin E 2 effect is 4 μM (Figure 4D ).…”

Section: Resultsmentioning

confidence: 99%

Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress

Endesh

Chuntharpursat‐Bon

Revill

et al. 2023

Liver International

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Background & AimsPIEZO1 and TRPV4 are mechanically and osmotically regulated calcium‐permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen.MethodsWall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non‐disruptive tag in native PIEZO1 or endothelial‐specific PIEZO1 deletion. Pharmacological agents were used to activate or inhibit PIEZO1, TRPV4 and associated pathways, including Yoda1 and Yoda2 for PIEZO1 and GSK1016790A for TRPV4 agonism, respectively.ResultsPIEZO1 activation leads to nitric oxide synthase‐ and endothelium‐dependent relaxation of the portal vein. TRPV4 activation causes contraction, which is also endothelium‐dependent but independent of nitric oxide synthase. The TRPV4‐mediated contraction is suppressed by inhibitors of phospholipase A2 and cyclooxygenases and mimicked by prostaglandin E2, suggesting mediation by arachidonic acid metabolism. TRPV4 antagonism inhibits the effect of agonising TRPV4 but not PIEZO1. Increased wall stretch and hypo‐osmolality inhibit TRPV4 responses while lacking effects on or amplifying PIEZO1 responses.ConclusionsThe portal vein contains independently functioning PIEZO1 channels and TRPV4 channels in the endothelium, the pharmacological activation of which leads to opposing effects of vessel relaxation (PIEZO1) and contraction (TRPV4). In mechanical and osmotic strain, the PIEZO1 mechanism dominates. Modulators of these channels could present important new opportunities for manipulating liver perfusion and regeneration in disease and surgical procedures.

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“…In agreement, AA was increased in the liver of colitis mice suggesting that GLA and DGLA are potentially used as precursors for AA production, skewing the DGLA/ AA balance to support inflammation (64, 65). Furthermore, this study putatively identified prostaglandin G2 (PGG2), an AA derivative, as being increased in the colitis liver and has been implicated as a pathophysiological factor in liver cirrhosis by promoting platelet aggregation and thrombosis (66). Therefore, the bidirectional liver-gut axis may exacerbate inflammation and tissue damage in both organs via AA production and conversion to small metabolites meaning the disappearance of the precursor GLA could be used as a biomarker of systemic disease progression (65, 67).…”

Section: Discussionmentioning

confidence: 99%

Spatial mapping of dextran sodium sulphate-induced intestinal inflammation and its systemic effects

Adams,

Rasid,

Hulme

et al. 2024

Preprint

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Inflammatory bowel disease (IBD) is a multifactorial disease and patients frequently experience extraintestinal manifestations affecting multiple sites. Causes of systemic inflammation remain poorly understood but molecules originating from the intestine likely play a role with microbial and host small molecules polarizing host immune cells towards a pro- or anti-inflammatory phenotype. Using the dextran sodium sulphate (DSS) mouse model, which mimics models the disrupted barrier function in IBD, microbial dysbiosis and immune cell dysregulation in IBD, we investigated metabolomic and phenotypic changes at intestinal and systemic sites. Through mass spectrometry imaging we mapped the spatial distribution and relative abundance of molecules and cell types across a range of tissues during colitis. This approach revealed specific molecular changes across a range of organs including the colon, ileum, liver, spleen and kidney, while no molecular changes were observed in the lungs of DSS-treated mice. Specific molecules, identified as contributing to the statistical separation of treated from control mice, were then spatially localized within organs to determine their effects on cellular phenotypes through imaging mass cytometry. Additionally, molecules that were significantly changed across multiple systemic sites in response to inflammation were identified. This spatial approach identified drivers of inflammation both locally in the intestine and systemically and has highlighted a number of molecules not previously implicated in inflammation linked to IBD or the systemic effects of intestinal inflammation. Together this data shows that gaining a better understanding of metabolic pathways and identifying molecular disease biomarkers within the intestine and systemic organs during IBD, might improve our understanding of disease aetiology and aid the development of new targeted therapies.

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Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis

Cited by 7 publications

References 34 publications

Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?

Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?

Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress

Spatial mapping of dextran sodium sulphate-induced intestinal inflammation and its systemic effects

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