Session Information
Date: Tuesday, November 12, 2019
Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III: Giant Cell Arteritis
Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Giant cell arteritis (GCA) is a systemic vasculitis affecting large vessels. The diagnosis is based on temporal artery biopsy (TAB) which shows an arterial infiltration accompanied by a destruction of the internal elastic layer of the media and a hyperplasia of the intima by proliferation of myofibroblasts. The origin of these myofibroblasts is controversial. Evidences suggest the activation of adventitial fibroblasts into myofibroblasts and their migration into the intima. The objective of this study was to determine whether adventitial fibroblasts migrate to the intima and thereby contribute to intimal hyperplasia during CGA.
Methods: Immunohistochemistry
Arterial sections from TAB of patients with GCA (n=24) and control subjects (n=24) were analyzed. Immunohistochemical analysis were performed using antibodies directed against fibroblasts (CD90, vimentin), myofibroblasts (alpha smooth muscle actin {ASMA}), vascular smooth muscle cells (desmin {VSMC}), prolyl-4-hydroxylase (collagen secretion activity {P4H}) and myosin (contraction activity). Stainings were quantified using ODPviewer® (Kamax Innovative System). Co-expression of CD90 with different stainings (ASMA, myosin and P4H) was also performed.
Culture cells
TABs were dissected to separate the adventitia from the other two layers (media and intima). Each fragment was seeded separately. Cells were identified by immunocytochemistry. Functional assays were performed using culture cells obtained from GCA patients’ TABs (n=8) and controls (n=7): proliferation (bromodeoxyuridine incorporation test), migration (scratch test) and invasion (boyden chamber). Several conditions were used: i) DMEM-Glutamax alone, ii) addition of 10% fetal bovine serum (FBS), iii) addition of platelet-derived growth factor (PDGF) to 40 ng/mL, iv) supernatants of cells.
Results: CD90 and vimentin (fibroblasts) were significantly higher in GCA than controls in adventitia and intima. ASMA (myofibroblasts) was significantly higher in the 3 tunics of patients with GCA. Expression of desmin (VSMC) was only present in the media for both groups. The adventitial and intimal CD90+ cells co-expressed ASMA, P4H and myosin more importantly during GCA.
Cultured cells from adventitia expressed CD90 and did not express desmin. These adventitial cells had an increased in vitro proliferation ability during GCA compared to controls in the presence of FCS, PDGF and fibroblast supernatants of control or GCA patients. Migration and invasion rates of these cells were also significantly increased during GCA in the presence of FCS or PDGF.
Conclusion: Vascular remodeling during GCA would start in the adventitial layer with a key role of fibroblasts. Adventitial fibroblasts could be activated into myofibroblasts and acquire proliferative and migratory abilities. They would participate in the intimal hyperplasia. Finally, the activating signal of adventitial fibroblasts into myofibroblasts is not yet known during GCA and requires further studies.
To cite this abstract in AMA style:
Parreau S, Vedrenne N, Régent A, Richard L, Sindou P, Mouthon L, Fauchais A, Jauberteau M, Ly K. Adventitial Fibroblast, an Important Actor in Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/adventitial-fibroblast-an-important-actor-in-giant-cell-arteritis/. Accessed .« Back to 2019 ACR/ARP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/adventitial-fibroblast-an-important-actor-in-giant-cell-arteritis/