title: Altered decorin leads to disrupted endothelial cell function: a possible mechanism in the pathogenesis of fetal growth restriction?
abstract: OBJECTIVE
  Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae.
  
  
  METHODS
  Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed.
  
  
  RESULTS
  DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies.
  
  
  CONCLUSIONS
  Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations.
authors.affiliation: NorthWest Academic Centre, The University of Melbourne and Sunshine Hospital, PO Box 294, 176 Furlong Road, St Albans 3021, Australia. Electronic address: akl.chui83@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Chui
authors.affiliation: Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, The University of Melbourne, Parkville 3052, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville 3052, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Murthi
authors.affiliation: NorthWest Academic Centre, The University of Melbourne and Sunshine Hospital, PO Box 294, 176 Furlong Road, St Albans 3021, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville 3052, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Gunatillake
authors.affiliation: Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, The University of Melbourne, Parkville 3052, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville 3052, Australia.
authors.forename: S P
authors.initials: SP
authors.lastname: Brennecke
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital and The University of Melbourne, Parkville 3052, Australia; Department of Clinical Haematology, The Royal Children's Hospital and The University of Melbourne, Parkville 3052, Australia; Department of Paediatrics, The Royal Children's Hospital and The University of Melbourne, Parkville 3052, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Ignjatovic
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital and The University of Melbourne, Parkville 3052, Australia; Department of Clinical Haematology, The Royal Children's Hospital and The University of Melbourne, Parkville 3052, Australia; Department of Paediatrics, The Royal Children's Hospital and The University of Melbourne, Parkville 3052, Australia.
authors.forename: P T
authors.initials: PT
authors.lastname: Monagle
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Kensington 2033, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Whitelock
authors.affiliation: NorthWest Academic Centre, The University of Melbourne and Sunshine Hospital, PO Box 294, 176 Furlong Road, St Albans 3021, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Said
mesh_terms: D017209:Apoptosis; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D058575:Decorin / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D034741:RNA, Small Interfering; D013917:Thrombin / Q000378:metabolism
chemical_list: C546878:DCN protein, human; D058575:Decorin; D034741:RNA, Small Interfering; D013917:Thrombin
keywords: Angiogenesis; Endothelial function; Gene expression; Regulation; Thrombosis