Abstract
IntroductionGiant 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.MethodsWe 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.ResultsWhereas 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0487-z) contains supplementary material, which is available to authorized users.
Highlights
Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels
Serum nerve growth factor (NGF) was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for brain-derived neurotrophic factor (BDNF) and NT-3
NGF and BDNF enhanced GCA-derived temporal artery vascular smooth muscle cell (VSMC) proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls
Summary
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 involved in the migration of vascular smooth muscle cells (VSMCs). Macrophages and giant cells produce platelet-derived growth factor (PDGF), which stimulates migration of vascular smooth muscle cells (VSMCs) from the media to the intima to initiate intimal hyperplasia. Neurotrophins (NTs) are growth factors initially described in the nervous system and include vascular cells [2]. NGF and BDNF and their two specific Trk receptors are involved in aortic intimal hyperplasia induced by balloon angioplasty in rats [3], while activation of p75NTR by NGF, NT-3 and, to a lesser extent, BDNF, induce VSMC apoptosis [5]
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