title: Impact of thrombosis on pulmonary endothelial injury and repair following sepsis.
abstract: The prevailing morbidity and mortality in sepsis are largely due to multiple organ dysfunction (MOD), most commonly lung injury, as well as renal and cardiac dysfunction. Despite recent advances in defining many aspects of the pathogenesis of sepsis-related MOD, including acute respiratory distress syndrome (ARDS), there are currently no effective pharmacological or cell-based treatments for the disease. Human and animal studies have shown that pulmonary thrombosis is common in sepsis-induced ARDS, and preclinical studies have shown that anticoagulation may improve outcome following sepsis challenge. The potential beneficial effect of anticoagulation on outcome is unconvincing in clinical studies, however, and these discrepancies may arise from the multiple and sometimes opposing actions of thrombosis on the pulmonary endothelium following sepsis. It has been suggested, for example, that mild pulmonary thrombosis prevents escape of bacterial infection into the circulation, while severe thrombosis causes hypoxia and results in pulmonary endothelial damage. Evidence from both human and animal studies has demonstrated the key role of microvascular leakage in determining the outcome of sepsis. In this review, we describe thrombosis-dependent mechanisms that regulate pulmonary endothelial injury and repair following sepsis, including activation of the coagulation cascade by tissue factor and stimulation of vascular repair by hypoxia-inducible factors. Targeting such mechanisms through anticoagulant, anti-inflammatory, and reparative methods may represent a novel approach for the treatment of septic patients.
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois; and.|Center for Lung and Vascular Biology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois.
authors.forename: Colin E
authors.initials: CE
authors.lastname: Evans
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois; and yyzhao@uic.edu.|Center for Lung and Vascular Biology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois.
authors.forename: You-Yang
authors.initials: YY
authors.lastname: Zhao
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D055370:Lung Injury / Q000209:etiology* / Q000473:pathology*; D008954:Models, Biological; D018805:Sepsis / Q000150:complications*; D013927:Thrombosis / Q000473:pathology*; D014945:Wound Healing
keywords: endothelium; injury; lung; repair; sepsis; thrombosis