PMID- 27784899
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Oct 27
TI  - Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level 
      correlates with severity and expression of EPCR-binding PfEMP1.
PG  - 35950
LID - 10.1038/srep35950 [doi]
LID - 35950
AB  - The pathogenesis of Plasmodium falciparum malaria involves a complex interplay 
      between parasite adhesion and inflammatory response that includes release of 
      cytokines and activation of the endothelium with accompanying release of 
      Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloproteinase 17 
      (ADAM17) is a protein responsible for releasing cytokines, including Tumor 
      Necrosis Factor alpha (TNFalpha), and shedding of adhesion proteins. In this study, we 
      show that plasma levels of ADAM17 are increased in Tanzanian children 
      hospitalized with a malaria infection compared with asymptomatic children but 
      similar to children hospitalized with other infectious diseases. The plasma 
      levels of ADAM17 decreased during recovery after an acute malaria episode. Plasma 
      levels of Ang2 were associated with markers of malaria severity and levels of var 
      transcripts encoding P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) 
      containing Cysteine Rich Inter Domain Region alpha1 (CIDRalpha1) domains predicted to 
      bind Endothelial Protein C receptor (EPCR). ADAM17 levels were not associated 
      with expression of var genes encoding different PfEMP1 types when controlling for 
      age. These data are the first to report ADAM17 plasma levels in malaria-exposed 
      individuals, and support the notion that parasite sequestration mediated by 
      EPCR-binding PfEMP1 is associated with endothelial activation and pathology in 
      severe paediatric malaria.
FAU - Petersen, Jens E V
AU  - Petersen JE
AD  - Centre for Medical Parasitology, Department of Immunology &Microbiology, Faculty 
      of Health and Medical Sciences, University of Copenhagen and Department of 
      Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
FAU - Mkumbaye, Sixbert I
AU  - Mkumbaye SI
AD  - Kilimanjaro Christian Medical University College and Kilimanjaro Clinical 
      Research Institute, Moshi, Tanzania.
FAU - Vaaben, Anna V
AU  - Vaaben AV
AD  - Centre for Medical Parasitology, Department of Immunology &Microbiology, Faculty 
      of Health and Medical Sciences, University of Copenhagen and Department of 
      Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
FAU - Manjurano, Alphaxard
AU  - Manjurano A
AD  - National Institute for Medical Research, Mwanza Research Centre, Mwanza, 
      Tanzania.
FAU - Lyimo, Eric
AU  - Lyimo E
AD  - National Institute for Medical Research, Mwanza Research Centre, Mwanza, 
      Tanzania.
FAU - Kavishe, Reginald A
AU  - Kavishe RA
AD  - Kilimanjaro Christian Medical University College and Kilimanjaro Clinical 
      Research Institute, Moshi, Tanzania.
FAU - Mwakalinga, Steven B
AU  - Mwakalinga SB
AD  - Kilimanjaro Christian Medical University College and Kilimanjaro Clinical 
      Research Institute, Moshi, Tanzania.
FAU - Mosha, Jacklin
AU  - Mosha J
AD  - National Institute for Medical Research, Mwanza Research Centre, Mwanza, 
      Tanzania.
FAU - Minja, Daniel T R
AU  - Minja DT
AD  - National Institute for Medical Research, Tanga Centre, Tanga, Tanzania.
FAU - Lusingu, John P A
AU  - Lusingu JP
AD  - National Institute for Medical Research, Tanga Centre, Tanga, Tanzania.
FAU - Theander, Thor G
AU  - Theander TG
AD  - Centre for Medical Parasitology, Department of Immunology &Microbiology, Faculty 
      of Health and Medical Sciences, University of Copenhagen and Department of 
      Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
FAU - Lavstsen, Thomas
AU  - Lavstsen T
AD  - Centre for Medical Parasitology, Department of Immunology &Microbiology, Faculty 
      of Health and Medical Sciences, University of Copenhagen and Department of 
      Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
FAU - Wang, Christian W
AU  - Wang CW
AD  - Centre for Medical Parasitology, Department of Immunology &Microbiology, Faculty 
      of Health and Medical Sciences, University of Copenhagen and Department of 
      Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
LA  - eng
GR  - R01 HL130678/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161027
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (ANGPT2 protein, human)
RN  - 0 (Angiopoietin-2)
RN  - 0 (Endothelial Protein C Receptor)
RN  - 0 (PROCR protein, human)
RN  - 0 (Protozoan Proteins)
RN  - 0 (erythrocyte membrane protein 1, Plasmodium falciparum)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM17 Protein/*blood
MH  - Adolescent
MH  - Angiopoietin-2/*blood
MH  - Child
MH  - Child, Preschool
MH  - Endothelial Protein C Receptor/*blood
MH  - Female
MH  - Gene Expression
MH  - Genes, Protozoan
MH  - Humans
MH  - Infant
MH  - Malaria, Falciparum/*blood/genetics/*parasitology
MH  - Male
MH  - Plasmodium falciparum/genetics
MH  - Protozoan Proteins/*blood/*genetics
MH  - Tanzania
PMC - PMC5082358
EDAT- 2016/10/28 06:00
MHDA- 2018/05/01 06:00
PMCR- 2016/10/27
CRDT- 2016/10/28 06:00
PHST- 2016/07/12 00:00 [received]
PHST- 2016/10/07 00:00 [accepted]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2016/10/28 06:00 [entrez]
PHST- 2016/10/27 00:00 [pmc-release]
AID - srep35950 [pii]
AID - 10.1038/srep35950 [doi]
PST - epublish
SO  - Sci Rep. 2016 Oct 27;6:35950. doi: 10.1038/srep35950.