Inhibition of the Biologic Activity of Tumor Necrosis Factor Maintains Vascular Endothelial Cell Function during Hyperdynamic Sepsis

Wang, Haichao; Tj, Wood; Zhou, Mian; Zf, Ba; Ih, Chaudry

doi:10.1097/00005373-199605000-00003

Cited by 25 publications

(7 citation statements)

References 28 publications

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“…Cellular damage is apparent as early as 15 min after LPS injection, with nuclear vacuolization, cytoplasmic swelling and protrusion, cytoplasmic fragmentation and detachment of the endothelium from its underlying layer. 33 In a caecal ligation and puncture rat sepsis model, similar events are seen after 10 h. 58 Circulating shed endothelial cells have also been identi®ed in human sepsis using antibodies to vWF and the VEGF receptor. 43 The number of circulating endothelial cells was higher in non-surviving patients than survivors.…”

Section: Infection and In¯ammationmentioning

confidence: 98%

Physiology of the endothelium

Galley

Webster

2004

British Journal of Anaesthesia

580

317

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In the past, the endothelium was considered to be inert, described as a 'layer of nucleated cellophane', with only non-reactive barrier properties, such as presentation of a non-thrombogenic surface for blood flow and guarding against pro-inflammatory insults. However, it is now becoming clear that endothelial cells actively and reactively participate in haemostasis and immune and inflammatory reactions. They regulate vascular tone via production of nitric oxide, endothelin and prostaglandins and are involved in the manifestations of atherogenesis, autoimmune diseases and infectious processes. They produce and react to various cytokines and adhesion molecules and it is now clear that they can mount anti- and pro-inflammatory and protective responses depending on environmental conditions and are key immunoreactive cells. Endothelial dysfunction or activation also contributes to a variety of disease states.

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Section: Infection and In¯ammationmentioning

confidence: 98%

Physiology of the endothelium

Galley

Webster

2004

British Journal of Anaesthesia

580

317

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“…Abnormal endothelial-dependent vascular relaxation is attributed to alteration of endothelial cell surface receptors, dysfunction of signal transduction pathways and downregulation and/or degradation of eNOS by pro-inflammatory cytokines such as TNF-, as well as by ROS/RNS or bacterial endotoxin [88]. In a model of septic shock, Wang et al [89] thus showed that inhibition of the biological activity of TNF-protects vascular endothelial cells' function. Finally, during sepsis, numerous stimuli potentially activate endothelium ATP-dependent potassium channels, like NO • or ONOO -, hypoxia, acidosis, or hyperlactatemia.…”

Section: Vasomotor Tone Abnormalitiesmentioning

confidence: 99%

Endothelial Dysfunction in Sepsis

Boisramé-Helms¹,

Kremer²,

Schini‐Kerth³

et al. 2013

Current Vascular Pharmacology

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The endothelium takes part in the regulation of numerous physiological functions and lies at the interface of circulating blood and the vessel wall. Under physiological conditions, it is responsible for anticoagulant and anti-adhesive properties, and it regulates vasomotor tone and vascular homeostasis. Endothelial dysfunction has been associated with many pathophysiological processes, such as inflammation and oxidative and nitrosative stresses. Endothelial cells are precociously exposed to circulating signaling molecules and physical stresses, like in sepsis and septic shock. Septic shock is associated with hypotension and frequently with disseminated intravascular coagulation contributing to multiple organ failure and a high mortality rate. Impairment of endothelial function leads to phenotypic and physical changes of the endothelium, with deregulated release of potent vasodilators nitric oxide and prostacyclin, reduction of vascular reactivity to vasoconstrictors, associated with leukocytes' and platelets' aggregation, and increase in inducible nitric oxide synthase expression that can exert a negative feedback on endothelial nitric oxide synthase expression, with subsequent deregulation of nitric oxide signaling. Endothelial dysfunction therefore plays a major role in the pathophysiology of septic shock and organ dysfunction, and has been suggested to be a predictor of mortality in sepsis. Thus, early detection of endothelial dysfunction could be of great interest to adapt treatment in initial stage of sepsis. Current therapeutics used in sepsis mostly aim at controlling inflammation, vascular function and coagulation. Fluid administration, vasopressors, vasodilators and recombinant human activated protein C are also part of the treatments with the ultimate goal to exert beneficial effects on organ function and survival.

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“…As early as 15 min after LPS injection [7] cellular injuries are apparent, with nuclear vacuolization, cytoplasmic swelling and protrusion, cytoplasmic fragmentation, and various degrees of detachment of the endothelium from its underlying layer. This can also be observed 10 hours after the onset of sepsis in a caecal ligation and puncture rat model [8]. Proinflammatory cytokines increase permeability of the Ecs, and this is manifested approximately 6 hours after inflammation is triggered and becomes maximal over 12-24 hours as the combination of cytokines exert potentiating effects [8,9].…”

Section: Endothelial Injurymentioning

confidence: 99%

“…This can also be observed 10 hours after the onset of sepsis in a caecal ligation and puncture rat model [8]. Proinflammatory cytokines increase permeability of the Ecs, and this is manifested approximately 6 hours after inflammation is triggered and becomes maximal over 12-24 hours as the combination of cytokines exert potentiating effects [8,9]. Endothelial physical disruption allows inflammatory fluid and cells to shift from the blood into the interstitial space.…”

Section: Endothelial Injurymentioning

confidence: 99%

Untitled

Vallet¹

2003

Crit Care

100

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During the past decade a unifying hypothesis has been developed to explain the vascular changes that occur in septic shock on the basis of the effect of inflammatory mediators on the vascular endothelium. The vascular endothelium plays a central role in the control of microvascular flow, and it has been proposed that widespread vascular endothelial activation, dysfunction and eventually injury occurs in septic shock, ultimately resulting in multiorgan failure. This has been characterized in various models of experimental septic shock. Now, direct and indirect evidence for endothelial cell alteration in humans during septic shock is emerging. The present review details recently published literature on this rapidly evolving topic.

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Inhibition of the Biologic Activity of Tumor Necrosis Factor Maintains Vascular Endothelial Cell Function during Hyperdynamic Sepsis

Cited by 25 publications

References 28 publications

Physiology of the endothelium

Physiology of the endothelium

Endothelial Dysfunction in Sepsis

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