title: Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling.
abstract: BACKGROUND
  Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.
  
  
  METHODS
  We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.
  
  
  RESULTS
  Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.
  
  
  CONCLUSIONS
  Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results.
authors.forename: Kim Heang
authors.initials: KH
authors.lastname: Ly
authors.forename: Alexis
authors.initials: A
authors.lastname: Régent
authors.forename: Elsa
authors.initials: E
authors.lastname: Molina
authors.forename: Sofiane
authors.initials: S
authors.lastname: Saada
authors.forename: Philippe
authors.initials: P
authors.lastname: Sindou
authors.forename: Claire
authors.initials: C
authors.lastname: Le-Jeunne
authors.forename: Antoine
authors.initials: A
authors.lastname: Brézin
authors.forename: Véronique
authors.initials: V
authors.lastname: Witko-Sarsat
authors.forename: François
authors.initials: F
authors.lastname: Labrousse
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Robert
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bourges
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Fauchais
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Vidal
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D013700:Giant Cell Arteritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D011446:Prospective Studies; D013699:Temporal Arteries / Q000378:metabolism* / Q000473:pathology; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D009414:Nerve Growth Factors