Redox Mechanisms of Vascular Cell Dysfunction in Sepsis

Author(s): L. C.P. Azevedo, M. Janiszewski, F. G. Soriano, F. R.M Laurindo

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 6 , Issue 2 , 2006

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Sepsis remains one of the leading causes of death in intensive care units, despite recent acquired knowledge on pathophysiology and treatment. Several mediators of inflammation and cellular damage have been implicated in the complex host-pathogen interaction underlying organ damage and multisystem organ failure , which are hallmarks of sepsis and common causes of death. Among such mediators, reactive oxygen/nitrogen species have been increasingly studied in the context of direct cytotoxicity as well as altered cell signaling. While the generation of reactive oxygen species by inflammatory cells in sepsis is well known, recent studies have shown that vascular cells are able to release reactive oxygen intermediates that may be associated with endothelial dysfunction of sepsis. These compounds can activate transcription factors such as NF-κB that sustain inflammatory process or enzymatic systems like poly(ADPribose) polymerase-1, which are involved in apoptosis and cytotoxicity of sepsis. Our laboratory recently showed that platelet-derived exosomes from septic patients carry components of a superoxide-producing NADPH oxidase and can, at least in vitro, induce apoptosis of endothelial and vascular smooth muscle cells by a ROS-dependent pathway. Taken together, these data show that reactive oxygen species are involved in cell signaling and organ injury in sepsis. Efforts must be made to identify the precise contribution of these factors in septic process, in order to clarify the mechanisms associated with the disease. This will certainly lead to discovery of therapeutic strategies that can help us to mitigate vascular dysfunction of sepsis.

Keywords: Sepsis, reactive oxygen species, superoxide, PARP, NADPH oxidase, exosomes, vascular dysfunction

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Article Details

Year: 2006
Page: [159 - 164]
Pages: 6
DOI: 10.2174/187153006777442431
Price: $65

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