Neurotrophins are expressed in giant-cell arteritis lesions and may contribute to vascular remodeling (Arthritis Research & Therapy)

IntroductionGiant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischemic 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 remodeling 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 VSMC. 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 ischemic 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 VSMCs proliferation and BDNF facilitated migration of temporal-artery VSMCs in patients with GCA compared to controls. Conclusion: Our results suggest that NTs and NTRs are involved in vascular remodeling 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.