Admission Angiopoietin Levels in Children With Septic Shock

Giuliano, John S.; Lahni, Patrick; Harmon, Kelli; Wong, Hector R.; Doughty, Lesley; Carcillo, Joseph A.; Zingarelli, Basilia; Sukhatme, Vikas P.; Parikh, Samir M.; Wheeler, Derek S.

doi:10.1097/shk.0b013e318123867b

Cited by 119 publications

(107 citation statements)

References 36 publications

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“…[21][22][23][24][25] No definite conclusion on a causal relationship of Ang-1 and Ang-2 levels and plasma leakage could be made in this observational study. Similar trends in Ang-1 and Ang-2 levels have been found in severe malaria and sepsis, 26,27 but in contrast to DHF/DSS and sepsis, plasma leakage is not a prominent feature of malaria. Differences in other mediators of vascular permeability, such as pro-inflammatory cytokines and angiogenic proteins and their soluble receptors, might account for these differences in vascular permeability.…”

Section: Discussionsupporting

confidence: 59%

Imbalance of Angiopoietin-1 and Angiopoetin-2 in Severe Dengue and Relationship with Thrombocytopenia, Endothelial Activation, and Vascular Stability

Michels¹,

Ven²,

Djamiatun³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. The pathogenesis of plasma leakage during dengue hemorrhagic fever/dengue shock syndrome (DHF/ DSS) is largely unknown. Angiopoietins are key regulators of vascular integrity: Angiopoietin-1 is stored in platelets and maintains vascular integrity, and endothelium-derived angiopoietin-2 promotes vascular leakage. We determined angiopoietin-1 and angiopoietin-2 levels in a cohort of children in Indonesia with DHF/DSS and related them to plasma leakage markers. Patients with DHF/DSS had reduced angiopoietin-1 and increased angiopoietin-2 plasma levels on the day of admission when compared with levels at discharge and in healthy controls. There was an inverse correlation between angiopoietin-1 and markers of plasma leakage and a positive correlation between angiopoietin-2 and markers of plasma leakage. Angiopoietin-1 levels followed the same trend as the soluble platelet activation marker P-selectin and correlated with platelet counts. Dengue-associated thrombocytopenia and endothelial activation are associated with an imbalance in angiopoietin-2: angiopoietin-1 plasma levels. This imbalance may contribute to the transient plasma leakage in DHF/DSS.

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Section: Discussionsupporting

confidence: 59%

Imbalance of Angiopoietin-1 and Angiopoetin-2 in Severe Dengue and Relationship with Thrombocytopenia, Endothelial Activation, and Vascular Stability

Michels¹,

Ven²,

Djamiatun³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…In fact, opposite regulation of these changes has been observed in the lungs of hypoxic rats, where Ang-3 expression is significantly induced, whereas that of Ang-1 expression is attenuated (1). Second, the fact that LPS injection elicits a significant upregulation of Ang-2 mRNA and protein in at least three organs implies that increased circulating levels of this protein in patients with severe sepsis may originate from more than one organ (8,23). Third, there is qualitative similarity in the responses of Ang-1 and VEGF expressions in the diaphragm to in vivo LPS administration, with the expression of both genes being induced within 6 h, followed by significant attenuation thereafter.…”

Section: Discussionmentioning

confidence: 96%

“…Note the decline in Ang-1 protein levels, whereas Ang-2 protein expression increased significantly in response to LPS administration. circulating Ang-2 levels in patients with severe sepsis and in children with septic shock, and by the observation that injection of Ang-2 protein in vivo elicits a significant increase in edema formation in the mouse paw (8,23,26). Finally, Ang-2-deficient mice have an impaired ability to express cytokine-inducible adhesion molecules on EC surfaces after inflammatory activation, further implicating Ang-2 in promoting inflammation (6).…”

Section: Discussionmentioning

confidence: 99%

Regulation of angiopoietin expression by bacterial lipopolysaccharide

Mofarrahi¹,

Nouh²,

Qureshi³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Angiopoietins are ligands for Tie-2 receptors and play important roles in angiogenesis and inflammation. While angiopoietin-1 (Ang-1) inhibits inflammatory responses, angiopoietin-2 (Ang-2) promotes cytokine production and vascular leakage. In this study, we evaluated in vivo and in vitro effects of Escherichia coli lipopolysaccharides (LPS) on angiopoietin expression. Wild-type C57/BL6 mice were injected with saline (control) or E. coli LPS (20 mg/ml ip) and killed 6, 12, and 24 h later. The diaphragm, lung, and liver were excised and assayed for mRNA and protein expression of Ang-1, Ang-2, and Tie-2 protein and tyrosine phosphorylation. LPS injection elicited a severalfold rise in Ang-2 mRNA and protein levels in the three organs. By comparison, both Ang-1 and Tie-2 levels in the diaphragm, liver, and lung were significantly attenuated by LPS administration. In addition, Tie-2 tyrosine phosphorylation in the lung was significantly reduced in response to LPS injection. In vitro exposure to E. coli LPS elicited cell-specific changes in Ang-1 expression, with significant induction in Ang-1 expression being observed in cultured human epithelial cells, whereas significant attenuation of Ang-1 expression was observed in response to E. coli LPS exposure in primary human skeletal myoblasts. In both cell types, E. coli LPS elicited substantial induction of Ang-2 mRNA, a response that was mediated in part through NF-κB. We conclude that in vivo endotoxemia triggers functional inhibition of the Ang-1/Tie-2 receptor pathway by reducing Ang-1 and Tie-2 expression and inducing Ang-2 levels and that this response may contribute to enhanced vascular leakage in sepsis.

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“…Circulating concentrations of Ang-2 are reported to be considerably increased in patients with sepsis, and their levels are related with disease severity (Giuliano et al, 2007;Orfanos et al, 2007;Kranidioti et al, 2009). It is unclear, however, whether this is a circumstantial association or there is a functional consequence of Ang-2 increased levels related to the course of the disease.…”

Section: Introductionmentioning

confidence: 87%