Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation

Miyashita, Tomoharu; Nakanuma, Shinichi; Ahmed, Ali; Makino, Isamu; Hayashi, Hironori; Oyama, Katsunobu; Nakagawara, Hisatoshi; Tajima, Hidehiro; Takamura, Hiroyuki; Ninomiya, Itasu; Fushida, Sachio; Harmon, John W.; Ohta, Tetsuo

doi:10.1007/s10353-015-0363-3

Cited by 45 publications

(46 citation statements)

References 58 publications

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“…Platelet aggregation during hepatic IRI represents an important mechanism by which IRI is potentiated after liver transplantation . LSEC injury causes increased adhesion of platelets through upregulation of P‐selectin.…”

Section: Cellular Mechanisms Of Liver Irimentioning

confidence: 99%

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Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Dar

Sullivan

Bynon

et al. 2019

Liver International

273

245

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Liver disease causing end organ failure is a growing cause of mortality. In most cases, the only therapy is liver transplantation. However, liver transplantation is a complex undertaking and its success is dependent on a number of factors. In particular, liver transplantation is subject to the risks of ischaemia‐reperfusion injury (IRI). Liver IRI has significant effects on the function of a liver after transplantation. The cellular and molecular mechanisms governing IRI in liver transplantation are numerous. They involve multiple cells types such as liver sinusoidal endothelial cells, hepatocytes, Kupffer cells, neutrophils and platelets acting via an interconnected network of molecular pathways such as activation of toll‐like receptor signalling, alterations in micro‐RNA expression, production of ROS, regulation of autophagy and activation of hypoxia‐inducible factors. Interestingly, the cellular and molecular events in liver IRI can be correlated with clinical risk factors for IRI in liver transplantation such as donor organ steatosis, ischaemic times, donor age, and donor and recipient coagulopathy. Thus, understanding the relationship of the clinical risk factors for liver IRI to the cellular and molecular mechanisms that govern it is critical to higher levels of success after liver transplantation. This in turn will help in the discovery of therapeutics for IRI in liver transplantation – a process that will lead to improved outcomes for patients suffering from end‐stage liver disease.

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Section: Cellular Mechanisms Of Liver Irimentioning

confidence: 99%

“…This process is termed extravasated platelet aggregation (EPA) . LSEC injury induces vasoconstriction in the sinusoids .…”

Section: Cellular Mechanisms Of Liver Irimentioning

confidence: 99%

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Dar

Sullivan

Bynon

et al. 2019

Liver International

273

245

View full text Add to dashboard Cite

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“…Such proteins risk causing tissue and endothelial damage as DAMPs (12,23). Furthermore, this damage associated with NETs contributes to denuding of the endothelium or loss of the fenestrations and endothelial detachment (10,11,24). In the liver tissue, sinusoidal endothelial cell damage allows platelets to enter the space of Disse, which contains collagen type 3 (24,25).…”

Section: Hande and Immunohistochemical Analysis For The Presence And Lomentioning

confidence: 99%

“…Furthermore, this damage associated with NETs contributes to denuding of the endothelium or loss of the fenestrations and endothelial detachment (10,11,24). In the liver tissue, sinusoidal endothelial cell damage allows platelets to enter the space of Disse, which contains collagen type 3 (24,25). Within the space of Disse, platelets bind to and form aggregates with the collagen type 3 (26).…”

Section: Hande and Immunohistochemical Analysis For The Presence And Lomentioning

confidence: 99%

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction

Sakurai

Miyashita

Okazaki

et al. 2017

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Abstract. Background Sepsis is a clinical syndrome of systemic inflammatory responses arising from an infectious process with a presumed or known focus (1, 2). Severe sepsis, defined as sepsis with acute organ dysfunction, is associated with high morbidity and mortality rates (3). Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis (4, 5). Sepsis-induced multiple organ failure (MOF) has numerous causes, such as various types of shock, adult respiratory distress syndrome (ARDS), and disseminated intravascular coagulation (DIC) (6). Gando et al. (7) reported that DIC is frequently associated with systemic inflammatory response syndrome (SIRS; 83%) and that such patients have a high mortality rate (63%). Ogura et al. (4) evaluated coagulation activity, organ dysfunction, and SIRS in critically-ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. In critically-ill patients with thrombocytopenia, they found that coagulopathy and organ dysfunction progressed with a significant mutual correlation, depending on the increase in SIRS scores. Thus, SIRSassociated coagulopathy may play a critical role in inducing organ dysfunction after severe insult. 1051This article is freely accessible online.Correspondence to: Tomoharu Miyashita,

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“…In case of rapid hepatocyte burst, sinusoidal endothelial cell injury extravasated platelet aggregation thromboxane A2, serotonin, transforming growth factor-beta and plasminogen activator inhibitor-1, released by EPA are important markers [172]. For nonalcoholic fatty liver disease stellate cells VD and transforming growth factors (TGF)-β are important markers [173].…”

Section: Therapeutic Role Of Cell Secreted Growth Factorsmentioning

confidence: 99%

Stem Cell Therapeutics of Acute Liver Diseases, Transplantation, and Regeneration

Upadhyay¹

2017

J Cell Sci Ther

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Present review article explains various causes of acute liver diseases and their therapeutics. This article describes major reasons of hepatic pathophysiological conditions and diseases including hepatitis, cholestasis, alcoholic and non-alcoholic steatohepatitis, jaundice, liver cirrhosis, carcinogenesis and many others. This article emphasizes use of proliferating hepatocytes, hepatic oval cells, adult human liver mesenchymal stem/progenitor cells, induced pluripotent stem cells (iPSCs) and hematopoietic stem cells in cell transplantation for restoration of liver structure and function. It also justified the therapeutic role of cell secreted growth factors and dietary factors required during natural healing and regeneration liver after surgery or liver transplantation. It sketches out regulatory roles of signaling pathways, expression of cell cycle regulators, growth factors, cytokines, and role of different mitogens in induction of liver stem/progenitor cells (LSPCs) after organ/stem cell transplantation. This article suggests a need for development of new advanced biomaterials, methods, technologies and stem cells for development of targeted therapies to combat and cure liver related diseases and disorders. This article also advice people for avoiding excessive use of alcohol, drugs, fats, salt, high energy diets, and iron as all are responsible of liver cirrhosis, damage and failure.

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Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation

Cited by 45 publications

References 58 publications

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction

Stem Cell Therapeutics of Acute Liver Diseases, Transplantation, and Regeneration

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