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Arthritis Research and Therapy

, 16:487

First Online: 24 November 2014Received: 24 March 2014Accepted: 10 November 2014

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 P75 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 p75 receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results.

AbbreviationsAbantibody

ACRAmerican College of Rheumatology

Aktprotein kinase B

BDNFbrain-derived neurotrophic factor

DMEMDulbecco’s modified Eagle’s medium

ELISAenzyme-linked immunosorbent assay

ERKextracellular signal-regulated kinase

FCSfoetal calf serum

FGFfibroblast growth factor

GCAgiant cell arteritis

HChealthy control

ILinterleukin

INFinterferon

NGFnerve growth factor

NTneurotrophin

NT-3neurotrophin-3

NTRneurotrophin receptor

PCRpolymerase chain reaction

PDGFplatelet-derived growth factor

RTreverse transcriptase

SEMstandard errors of the mean

TAtemporal artery

TABtemporal artery biopsy

TASMCtemporal artery VSMC

TNF-αtumour necrosis factor alpha

Trktropomyosin receptor kinase

VSMCvascular smooth muscle cell

Electronic supplementary materialThe online version of this article doi:10.1186-s13075-014-0487-z contains supplementary material, which is available to authorized users.

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Autor: Kim Heang Ly - Alexis Régent - Elsa Molina - Sofiane Saada - Philippe Sindou - Claire Le-Jeunne - Antoine Brézin - Véro

Fuente: https://link.springer.com/







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