Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling

Kim Heang Ly (1, 2) , Alexis Régent (3) , Elsa Molina (2) , Sofiane Saada (2) , Philippe Sindou (2) , Claire Le-Jeunne (4) , Antoine Brézin (5) , Véronique Witko-Sarsat (3) , François Labrousse (2) , Pierre-Yves Robert (6) , Philippe Bertin (7) , Jean-Louis Bourges (4) , Anne-Laure Fauchais (2) , Elisabeth Vidal (8) , Luc Mouthon (3) , Marie-Odile Jauberteau (2, 9)

1 Service de Médecine interne A et polyclinique médicale [CHU Limoges]
2 HCP - Homéostasie Cellulaire et Pathologies
3 IC UM3 (UMR 8104 / U1016) - Institut Cochin
4 Hôpital Hôtel-Dieu [Paris]
5 Hôpital Cochin [AP-HP]
6 Service d'Ophtalmologie [CHU Limoges]
7 Orange Labs [Cesson-Sévigné]
8 CHU Limoges
9 Service d'Immunologie et immunogénétique [CHU Limoges]

Introduction: 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.

Mots clés: Giant Cell Arteritis; Vascular Remodelling; Temporal Artery; Intimal Hyperplasia; Nerve Growth Factor

Domaines: Cardiologie et système cardiovasculaire; Biologie cellulaire

Kim Heang Ly, Alexis Régent, Elsa Molina, Sofiane Saada, Philippe Sindou, et al.. Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling. Arthritis Research and Therapy, 2014, 16 (6), pp.487. ⟨10.1186/s13075-014-0487-z⟩. ⟨hal-01827717⟩