title: Imbalance of angiopoietin-1 and angiopoetin-2 in severe dengue and relationship with thrombocytopenia, endothelial activation, and vascular stability.
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.
authors.affiliation: Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. m.michels@aig.umcn.nl
authors.forename: Meta
authors.initials: M
authors.lastname: Michels
authors.forename: André J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Kis
authors.initials: K
authors.lastname: Djamiatun
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
authors.forename: Silvie
authors.initials: S
authors.lastname: Sebastian
authors.forename: Sultana M H
authors.initials: SM
authors.lastname: Faradz
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
mesh_terms: D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002199:Capillary Permeability; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003715:Dengue / Q000097:blood* / Q000150:complications; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D013921:Thrombocytopenia / Q000097:blood* / Q000150:complications
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers