Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Giant cell arteritis (GCA) is a large-vessels vasculitis. Hhistopathological findings show cellular infiltrates, internal elastic lumina disruption and intimal hyperplasia leading to luminal stenosis. Platelet-derived growth factor (PDGF) stimulates vascular smooth muscle cells (VSMC) migration from the media to the intima initiating intimal hyperplasia. Neurotrophins (NTs) and their receptors (NTRs) belong to a family of growth factors, described in nervous system. They include the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). NTR include: the selective tropomyosin receptor kinase (Trk), TrkA for NGF, TrkB for BDNF and TrkC for NT-3, and a non-selective receptor p75NTR and a co-receptor, which is almost associated with p75NTR, called sortilin. NTs and NTRs are involved in cardiovascular development, blood vessel growth and VSMC functions. We hypothesized that NTs and NTRs are involved in the vascular remodeling stage of GCA.
Methods: We included consecutive patients who underwent temporal artery biopsy (TAB) for a suspicion of GCA. We develop an enzymatic digestion method to obtain VSMC from TAB (TASMC). TASMC from six GCA patients and 10 controls were used to study NT and NTR involvement in vascular remodeling of GCA.
Results: NGF, BDNF and sortilin were significantly overexpressed in GCA patients (n=22) compared to controls (n=21). NT-3 and p75NTR were only expressed in GCA patients. An overexpression of TrkB receptor was noted in GCA patients with ischemic complications. NT-3, TrkB, TrkC and sortilin trancripts were overexpressed (increase upper fivefold levels) in TASMC from GCA patients compared to controls. NTs stimulated TASMC proliferation, similarly to FCS (10%) at day 3 in both groups, this effect tended to disappear at day 4. The p75NTR blocking alone tend to decrease cell proliferation at day 3, especially in GCA patients TASMC (p=0.053). TASMC from GCA patients were significantly able to migrate in presence of exogenous BDNF in comparison to those from controls after a 24-hour exposure. Only cells from GCA were able to significantly invade matrigel chambers in presence of 10% FCS and exogenous PDGF. NGF sera concentrations were significantly higher in 30 patients with proven GCA compared to 48 controls (177 +/- 67.6 pg/mL vs 145.5 +/- 66 pg/mL, p=0.04) .
Conclusion: Herein, we report for the first time, the expression and functions of NTs and their receptors, potentially involved in vascular remodelling in GCA. It is worth noting that NGF, BDNF and sortilin are significantly overexpressed in different histological layers of TA in GCA patients compared to those of controls. In addition, TrkB staining was significantly higher in TA of GCA patients with cranial ischemic events. BDNF enhances TASMC migration by binding to TrkB and p75NTR receptor. Our results provide new insight concerning NTs and their receptors in the vascular remodelling stage of GCA pathogenesis. Their overexpression could contribute to intimal hyperplasia by facilitating VSMC migration from media to intima. However further studies will be conducted to elucidate signalling pathways that allow VSMC migration in order to define new therapeutic approach in patients with GCA
Disclosure:
K. H. Ly,
None;
A. Régent,
None;
E. Molina,
None;
S. Saada,
None;
P. Sindou,
None;
C. Le Jeunne,
None;
A. Brezin,
None;
V. witko-Sarsat,
None;
P. Bertin,
None;
F. Labrousse,
None;
P. Y. Robert,
None;
A. L. Fauchais,
None;
E. Vidal,
None;
L. Mouthon,
None;
M. O. Jauberteau,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neurotrophins-are-involved-in-vascular-remodeling-of-giant-cell-arteritis/