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

Abstract

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.

Important of Angiopoietic System in Evaluation of Endothelial Damage in Children with Crimean–Congo Hemorrhagic Fever

“…7 They commented this finding as an Ang/Tie imbalance and inducing the plasma leakage. 36 Our results supports this statement.…”

Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage

“…We previously reported that Ang-1 levels are also lower in dengue infection. 31 Plasma Ang-1 acts through the Tie-2 receptor, which is not expressed on post-capillary venules. 32 These venules are an important site for plasma leakage.…”

Pathogenesis of Dengue Thrombocytopenia: Prospective Challenges for Researchers

“…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 [10].…”

“…The existing laboratory tests to monitor abnormal host response [10][11][12] are complex, costly and require sophisticated laboratory infrastructure and trained personnel. Researchers should standardize 1-2 step in vitro assays which can be carried out in non-academic, non-research health centres.…”