title: Changes in biomarkers after therapeutic intervention in temporal arteries cultured in Matrigel: a new model for preclinical studies in giant-cell arteritis.
abstract: BACKGROUND
  Search for therapeutic targets in giant-cell arteritis (GCA) is hampered by the scarcity of functional systems. We developed a new model consisting of temporal artery culture in tri-dimensional matrix and assessed changes in biomarkers induced by glucocorticoid treatment.
  
  
  METHODS
  Temporal artery sections from 28 patients with GCA and 22 controls were cultured in Matrigel for 5 days in the presence or the absence of dexamethasone. Tissue mRNA concentrations of pro-inflammatory mediators and vascular remodelling molecules was assessed by real-time RT-PCR. Soluble molecules were measured in the supernatant fluid by immunoassay.
  
  
  RESULTS
  Histopathological features were exquisitely preserved in cultured arteries. mRNA concentrations of pro-inflammatory cytokines (particularly IL-1β and IFNγ), chemokines (CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES) and MMP-9 as well as IL-1β and MMP-9 protein concentrations in the supernatants were significantly higher in cultured arteries from patients compared with control arteries. The culture system itself upregulated expression of cytokines and vascular remodelling factors in control arteries. This minimised differences between patients and controls but underlines the relevance of changes observed. Dexamethasone downregulated pro-inflammatory mediator (IL-1β, IL-6, TNFα, IFNγ, MMP-9, TIMP-1, CCL3 and CXCL8) mRNAs but did not modify expression of vascular remodelling factors (platelet derived growth factor, MMP-2 and collagens I and III).
  
  
  CONCLUSIONS
  Differences in gene expression in temporal arteries from patients and controls are preserved during temporal artery culture in tri-dimensional matrix. Changes in biomarkers elicited by glucocorticoid treatment satisfactorily parallel results obtained in vivo. This may be a suitable model to explore pathogenetic pathways and to perform preclinical studies with new therapeutic agents.
authors.affiliation: Vasculitis Research Unit, Department of Systemic Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), , Barcelona, Catalonia, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Corbera-Bellalta
authors.forename: Ana
authors.initials: A
authors.lastname: García-Martínez
authors.forename: Ester
authors.initials: E
authors.lastname: Lozano
authors.forename: Ester
authors.initials: E
authors.lastname: Planas-Rigol
authors.forename: Itziar
authors.initials: I
authors.lastname: Tavera-Bahillo
authors.forename: Marco A
authors.initials: MA
authors.lastname: Alba
authors.forename: Sergio
authors.initials: S
authors.lastname: Prieto-González
authors.forename: Montserrat
authors.initials: M
authors.lastname: Butjosa
authors.forename: Georgina
authors.initials: G
authors.lastname: Espígol-Frigolé
authors.forename: José
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Fernández
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux-Lombard
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
authors.forename: Mahboob U
authors.initials: MU
authors.lastname: Rahman
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cid
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003094:Collagen; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D013700:Giant Cell Arteritis / Q000378:metabolism / Q000473:pathology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007797:Laminin; D008954:Models, Biological; D011509:Proteoglycans; D012333:RNA, Messenger / Q000235:genetics; D013699:Temporal Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques / Q000379:methods
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004338:Drug Combinations; D005938:Glucocorticoids; D018836:Inflammation Mediators; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003907:Dexamethasone; D003094:Collagen
keywords: Chemokines; Corticosteroids; Cytokines; Giant Cell Arteritis; Systemic vasculitis