Endothelial Dysfunction in Sepsis

Abstract

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.

Effects of Ecballium elaterium on brain in a rat model of sepsis-associated encephalopathy

“…The understanding of underlying mechanisms of sepsis has been improving [15]. Inflammatory response, which is induced by sepsis, may cause serious organ dysfunctions where endothelial injury plays a pivotal role [16]. As well as being a gatekeeper between blood and tissues, endothelium also exerts many functions in anti-inflammatory and anti-oxidant defense.…”

“…As well as being a gatekeeper between blood and tissues, endothelium also exerts many functions in anti-inflammatory and anti-oxidant defense. Bacterial toxins and oxidative stress disturb endothelial integrity [15,16]. This results in incresed permeability of the blood-brain barrier and brain edema, which may distort microcirculation.…”

Disseminated Intravascular Coagulation in Obstetrics: Ethiopathogenesis and up to date Management Strategies

“…Studies done showed that endothelial dysfunction plays a key role in the pathophysiology of septic abortion (20) .…”

The Bacterial Component Flagellin Induces Anti-Sepsis Protection Through TLR-5, IL-1RN and VCAN During Polymicrobial Sepsis in Mice

“…Dysregulation of the innate immune system during sepsis leads to inflammatory signal amplification upon cellular recognition of bacterial products. Sepsis is characterized by abnormal leukocyte activation, severe endothelial injuries, and ultimately organ failure due to septic shock [1].…”