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dc.contributor.authorKarki, Pratap
dc.contributor.authorBirukov, Konstantin G.
dc.contributor.authorBirukova, Anna A.
dc.date.accessioned2020-11-18T18:34:04Z
dc.date.available2020-11-18T18:34:04Z
dc.date.issued2020-10-13
dc.identifier.urihttp://hdl.handle.net/10713/14117
dc.description.abstractExtracellular histones released from injured or dying cells following trauma and other severe insults can act as potent damage-associated molecular patterns. In fact, elevated levels of histones are present in human circulation in hyperinflammatory states such as acute respiratory distress syndrome and sepsis. The molecular mechanisms owing to histone-induced pathologies are at the very beginning of elucidating. However, neutralization of histones with antibodies, histone-binding or histone-degrading proteins, and heparan sulfates have shown promising therapeutic effects in pre-clinical acute respiratory distress syndrome and sepsis models. Various cell types undergoing necrosis and apoptosis or activated neutrophils forming neutrophil extracellular traps have been implicated in excessive release of histones which further augments tissue injury and may culminate in multiple organ failure. At the molecular level, an uncontrolled inflammatory cascade has been considered as the major event; however, histone-activated coagulation and thrombosis represent additional pathologic events reflecting coagulopathy. Furthermore, epigenetic regulation and chemical modifications of circulating histones appear to be critically important in their biological functions as evidenced by increased cytotoxicity associated with citrullinated histone. Herein, we will briefly review the current knowledge on the role of histones in acute respiratory distress syndrome and sepsis, and discuss the future potential of anti-histone therapy for treatment of these life-threatening disorders.en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.urihttps://doi.org/10.1177/2045894020965357en_US
dc.language.isoenen_US
dc.publisherSAGE Publications Inc.en_US
dc.relation.ispartofPulmonary Circulationen_US
dc.subjectacute respiratory distress syndrome (ARDS)en_US
dc.subjectcoagulationen_US
dc.subjectendothelial dysfunctionen_US
dc.subjecthistonesen_US
dc.subjectlung injuryen_US
dc.subjectsepsisen_US
dc.titleExtracellular histones in lung dysfunction: a new biomarker and therapeutic target?en_US
dc.typeArticleen_US
dc.identifier.doi10.1177/2045894020965357
dc.source.volume10
dc.source.issue4


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