Title:Endothelial Dysfunction in Sepsis
Volume: 11
Issue: 2
Author(s): Julie Boisrame-Helms, Helene Kremer, Valerie Schini-Kerth and Ferhat Meziani
Affiliation:
Keywords:
Endothelial dysfunction, inflammation, oxidative stress, sepsis, hypotension, vascular function
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.
