title: Dysregulated post-transcriptional control of COX-2 gene expression in gestational diabetic endothelial cells.
abstract: OBJECTIVE
  Hyperglycaemic memory describes the progression of diabetic complications during subsequent periods of improved glycaemia. We addressed the hypothesis that transient hyperglycaemia causes aberrant COX-2 expression in HUVEC in response to IL-1β through the induction of long-lasting epigenetic changes involving microRNA-16 (miR-16), a post-transcriptional modulator of COX-2 expression.
  
  
  METHODS
  Studies were performed on HUVEC collected from women with gestational diabetes mellitus (GDM) (dHUVEC) and normal women (nHUVEC).
  
  
  RESULTS
  In dHUVEC treated with IL-1β, the expression of COX-2 mRNA and protein was enhanced and generation of prostanoids increased (the most abundant was the promitogenic PGF2α). COX-2 mRNA was more stable in dHUVEC and this was associated with miR-16 down-regulation and c-Myc induction (a suppressor of miR expression). dHUVEC showed increased proliferation in response to IL-1β, which was prevented by a COX-2 inhibitor and PGF2αreceptor antagonist. Comparable changes in COX-2 mRNA, miR-16 and c-Myc detected in dHUVEC were produced in nHUVEC exposed to transient high glucose and then stimulated with IL-1β under physiological glucose levels; superoxide anion production was enhanced under these experimental conditions.
  
  
  CONCLUSIONS
  Our results describe a possible mechanism operating in GDM that links the enhanced superoxide anion production and epigenetic changes, associated with hyperglycaemic memory, to endothelial dysfunction through dysregulated post-transcriptional control of COX-2 gene expression in response to inflammatory stimuli. The association of conventional therapy for glycaemic control with agents affecting inflammatory responses and oxidative stress might lead to a more effective prevention of the complications associated with GDM.
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Di Francesco
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Dovizio
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Trenti
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcantoni
authors.affiliation: Department of Cancer Biology, University of Kansas Cancer Center, Kansas City, KS, USA.
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Moore
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute, UCD, Dublin, Ireland.
authors.forename: Peadar
authors.initials: P
authors.lastname: O'Gaora
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute, UCD, Dublin, Ireland.
authors.forename: Cathal
authors.initials: C
authors.lastname: McCarthy
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tacconelli
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bruno
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Alberti
authors.affiliation: Department of Women's and Children's Health, University of Padua, Padua, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gizzo
authors.affiliation: Department of Women's and Children's Health, University of Padua, Padua, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Nardelli
authors.affiliation: E. MEDEA Scientific Institute, Conegliano, Treviso, Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Orso
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute, UCD, Dublin, Ireland.
authors.forename: Orina
authors.initials: O
authors.lastname: Belton
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Trevisi
authors.affiliation: Department of Cancer Biology, University of Kansas Cancer Center, Kansas City, KS, USA.
authors.forename: Dan A
authors.initials: DA
authors.lastname: Dixon
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Patrignani