title: Association Between Angiopoietin-2 and Enterovirus 71 Induced Pulmonary Edema.
abstract: OBJECTIVE
  To characterize pulmonary edema (PE) fluid induced by enterovirus 71 (EV71) infection, elucidate the relationship between angiopoietin-2 (Ang-2) and PE, and explore the pathogenesis of PE.
  
  
  METHODS
  Clinical data were collected from critical infants with EV71 infection. The infants were grouped into PE, non-PE, and control groups. The control group included infants in the preoperative period of elective inguinal hernia surgery. Biochemical changes in PE fluid were evaluated, and Ang-2 levels in serum and PE fluid were measured. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with serum from the control and PE groups and human recombinant Ang-2 or serum from the PE group and human recombinant Ang-1, and changes in the intercellular junctions were recorded via immunofluorescence.
  
  
  RESULTS
  Of the 161 infants with critical EV71 infection admitted to the hospital, 39 had PE. PE fluid was collected from 18 of these infants. The PE fluid-to-serum (P/S) ratio of total protein was 0.9 ± 0.2, and all P/S ratios of albumin were 1.0 ± 0.3. The Ang-2 level was higher in the non-PE group (333.2 ± 79.7 pg/ml) than in the control group (199.9 ± 26.7 pg/ml), although without statistical significance (P = 0.115). The Ang-2 level in the PE group (2819.2 ± 908.7 pg/ml) was higher than those in both the non-PE and the control groups (both, P < 0.001). Serum samples from the PE group had damaged cell junctions of confluent HPMEC monolayers that were reversed by Ang-1.
  
  
  CONCLUSIONS
  The PE fluid of infants with EV71-induced PE was protein-rich, and elevated Ang-2 expression was associated with PE. The mechanism through which PE develops may be related to Ang-2-induced cell junction damage.
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Zhijiang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hao
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China.
authors.forename: Fuju
authors.initials: F
authors.lastname: Zhuang
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256600, China. hxicuwxz@163.com.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Wang
mesh_terms: D042683:Angiopoietin-1 / Q000032:analysis / Q000378:metabolism; D042702:Angiopoietin-2 / Q000032:analysis / Q000378:metabolism; D002199:Capillary Permeability; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000628:therapy; D029821:Enterovirus A, Human / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000150:complications / Q000821:virology; D018495:Fluid Shifts; D006801:Humans; D007223:Infant; D011654:Pulmonary Edema / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D013396:Suction / Q000379:methods
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2
keywords: Angiopoietin-2; Endothelial intercellular junctions; Enterovirus 71; Pulmonary edema fluid