The role of platelet mediated thromboinflammation in acute liver injury

Morris, Sean Michael; Chauhan, Abhishek

doi:10.3389/fimmu.2022.1037645

Cited by 16 publications

(12 citation statements)

References 170 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, in cluster 4, to which tacrine and nitrofurazone belong, platelet aggregation was detected as a characteristic gene ontology term, particularly in the early time points ( Figure 5C ). Platelets are known to release signaling factors related to liver injury and regeneration, and their association with acute liver failure and liver disease has been reported (Morris and Chauhan, 2022). Their importance has also been suggested in mouse models of drug-induced liver injury (Chauhan et al ., 2020; Miyakawa et al ., 2015).…”

Section: Resultsmentioning

confidence: 99%

Rat Deconvolution as Knowledge Miner for Immune Cell Trafficking from Toxicogenomics Databases

Morita

Mizuno

Azuma

et al. 2023

Preprint

View full text Add to dashboard Cite

Toxicogenomics databases are useful for understanding biological responses in individuals because they are derived from well-controlled experiments and include a diverse spectrum of biological responses. Although these database contain no information regarding immune cells in the liver, which are important in the progression of liver injury, deconvolution that estimates cell-type proportions from bulk transcriptome could add information regarding immune cell trafficking to the database. However, deconvolution has been mainly applied to humans and mice and less often to rats, which are the main target of toxicogenomics databases. Here, we developed a deconvolution method for rats and established a methodology to obtain information regarding immune cells from toxicogenomics databases. The contributions of this work are three-fold. First, we obtained the gene expression profiles of various rat immune cells necessary for deconvolution and constructed a dataset; second, we compared the accuracy of models based on human and mouse datasets and showed the impact of species differences on deconvolution; third, we showed that rat deconvolution could retrieve information regarding immune cell trafficking from toxicogenomics databases.

show abstract

Section: Resultsmentioning

confidence: 99%

Rat Deconvolution as Knowledge Miner for Immune Cell Trafficking from Toxicogenomics Databases

Morita

Mizuno

Azuma

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In cases of acute liver injury, thromboinflammation-mediated liver damage with deposition of platelet-rich thrombi within hepatic sinusoids (30) has been reported. Therefore we measured circulating vWF and PECAM-1.…”

Section: Discussionmentioning

confidence: 99%

Liver Elastography in Acute Liver Failure: A Pilot Study

Trovato,

Artru,

Miquel

et al. 2024

Critical Care Explorations

View full text Add to dashboard Cite

OBJECTIVES: We aimed to assess the feasibility and reliability of sequential ultrasonographic and elastographic monitoring in acute liver failure (ALF). DESIGN: Observational study. SETTING: ALF is a rare, life-threatening disease that requires intensive care admission and often liver transplant, where the accurate selection of patients is crucial. Liver elastography is a noninvasive tool that can measure hepatic stiffness, but previous results have been inconclusive in ALF. PATIENTS: Patients admitted between October 2021 and March 2023 to the Liver Intensive Therapy Unit at King’s College Hospital with ALF were recruited, with healthy control (HC) individuals and acute-on-chronic liver failure (ACLF) used as controls. INTERVENTION: None. MEASUREMENTS: Average shear wave velocity was recorded with ElastPQ on the right and left liver lobes and the spleen. Portal vein flow, hepatic artery resistive index, and peak systolic velocity were also recorded. Physiologic and histologic data were used for comparison. MAIN RESULTS: Forty patients with ALF, 22 patients with ACLF, and 9 HC individuals were included in the study. At admission, liver stiffness measurement (LSM) of the right lobe was statistically different between HC individuals (5.6 ± 2 kPa), ALF (31.7 ± 17 kPa), and ACLF (76.3 ± 71 kPa) patients (ALF vs. ACLF, p = 0.0301). Spleen size and stiffness discriminated between ALF (10.4 ± 2 cm and 21.4 ± 16.6 kPa) and ACLF (14 ± 2.3 cm and 42.6 ± 26 kPa). At admission, LSM was not different between ALF patients who spontaneously survived versus patients who died or were transplanted in the following 90 days. However, the trend over the first 10 days of admission was different with a peak of LSM at day 5 in spontaneous survivors followed by reduction during the recovery phase. ALF patients with poor prognosis showed a persistently increased LSM. CONCLUSIONS: In ALF stiffness peaks at day 5 of admission with subsequent reduction in patients spontaneously surviving, showing significant difference according to the prognosis at day 7 of admission. LSM might be useful in distinguishing acute from acute-on-chronic liver failure together with spleen volume and stiffness.

show abstract

“…Platelets form aggregates with leukocytes, especially at sites of endothelial inflammation, which causes a disturbance of microcirculation and increased platelet consumption in the blood, resulting in thrombocytopenia [ 63 ]. Likewise, it has also been shown in various models of acute liver failure that activated platelets reduce sinusoidal blood flow through the secretion of vasoactive mediators and promote the development of inflammatory intrahepatic microthrombosis [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans

Tietze,

Christ,

et al. 2024

Cells

View full text Add to dashboard Cite

Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream transforming growth factor-β3, and perturbation of liver tissue homeostasis. All these events were ameliorated by hepatic transfusion of human bone marrow-derived MSCs. Treatment attenuated platelet and macrophage recruitment to the liver, both major sources of THBS1. By mitigating THBS1, MSCs muted surgery-induced tissue deterioration and dysfunction, and thus supported post-hepatectomy regeneration. After liver surgery, patients displayed increased tissue THBS1, which is associated with functional impairment and may indicate a higher risk of post-surgery complications. Since liver dysfunction involving THBS1 improves with MSC treatment in various animal models, it seems feasible to also modulate THBS1 in humans to impede post-surgery acute liver failure.

show abstract

The role of platelet mediated thromboinflammation in acute liver injury

Cited by 16 publications

References 170 publications

Rat Deconvolution as Knowledge Miner for Immune Cell Trafficking from Toxicogenomics Databases

Rat Deconvolution as Knowledge Miner for Immune Cell Trafficking from Toxicogenomics Databases

Liver Elastography in Acute Liver Failure: A Pilot Study

Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans

Contact Info

Product

Resources

About