Περίληψη:
Objective: Angiopoietin (Ang)-2 is an endothelium-specific growth
factor, regulated by proinflammatory stimuli, that destabilizes vascular
endothelium and increases vascular leakage; consequently, Ang-2 may
contribute to sepsis pathophysiology. We have studied 1) serum Ang-2
levels in critically-ill patients and investigated potential
relationships with inflammatory mediators and indices of disease
severity and 2) the effect of sepsis-related inflammatory mediators on
Ang-2 production by lung endothelium in vitro.
Design. Prospective clinical study followed by cell culture studies.
Setting. General intensive care unit and research laboratory of a
university hospital. Subjects: Human and bovine lung microvascular
endothelial cells and 61 patients (32 men). Patients were grouped
according to their septic stage as having: no systemic inflammatory
response syndrome (n = 6), systemic inflammatory response syndrome (n =
8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13).
Interventions. Cells were exposed to lipopolysaccharide, tumor necrosis
factor-alpha, and interleukin-6.
Measurements and Main Results., Patients’ serum Ang-2 levels were
significantly increased in severe sepsis as compared with patients with
no systemic inflammatory response syndrome or sepsis (p <.05 by analysis
of variance). Positive linear relationships were observed with: serum
tumor necrosis factor-alpha (r(s) = 0.654, p <.001), serum interleukin-6
(r(s) = 0.464, p <.001), Acute Physiology and Chronic Health Evaluation
II score (r(s) = 0.387, p <.001), and Sequential Organ Failure
Assessment score (r(s) = 0.428, p <.001). Multiple regression analysis
revealed that serum Ang-2 is mostly related to serum tumor necrosis
factor-alpha and severe sepsis. Treatment of human lung microvascular
endothelial cells with all mediators resulted in a
concentration-dependent Ang-2 reduction. Treatment of bovine lung
microvascular endothelial cells with lipopolysaccharide and tumor
necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced
basal Ang-2 levels.
Conclusions., First, patients’ serum Ang-2 levels are increased during
severe sepsis and associated with disease severity. The strong
relationship of serum Ang-2 with serum tumor necrosis factor-alpha
suggests that the latter may participate in the regulation of Ang-2
production in sepsis. Second, inflammatory mediators reduce Ang-2
release from human lung microvascular endothelial cells, implying that
this vascular bed may not be the source of increased Ang-2 in human
sepsis.
Συγγραφείς:
Orfanos, Stylianos E.
Kotanidou, Anastasia
Glynos, Constantinos
and Athanasiou, Chariclea
Tsigkos, Stelios
Dimopoulou, Ioanna
and Sotiropoulou, Christina
Zakynthinos, Spyros
Armaganidis,
Apostolos
Papapetropoulos, Andreas
Roussos, Charis
