Session Information
Date: Tuesday, November 14, 2023
Title: (2387–2424) Vasculitis – Non-ANCA-Associated & Related Disorders Poster III
Session Type: Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. So far, no studies have investigated adequately this question. The current study aims to identify the various senescent cell types in temporal artery biopsies (TABs) of GCA and polymyalgia rheumatica (PMR) patients by applying the novel multi-marker algorithm, define the secretory associated senescent phenotype (SASP) key molecules and explore possible implications of senescence in GCA pathogenesis.
Methods: Seventy five positive TABs from GCA patients and 22 negative from PMR patients were retrospectively analyzed. Senescent cells and their histologic origin were identified after staining for specific cellular markers including GL13, p21, vimentin, CD68, CD3 and aSMA, following the established multi-marker algorithm(1,2); IL-6 and MMP-9 were investigated as components of the (SASP) by triple co-staining. Twenty-four hour GCA or PMR artery culture supernatants were applied to primary skin fibroblasts with or without IL-6 blocking agent to explore the induction of IL-6 associated cellular senescence.
Results: Senescent cells were present in GCA arteries at higher proportion compared to PMR (9.50% vs 2.66% respectively, p< 0.0001) adjacent to the inflammatory cells and were mainly originated from fibroblasts (29.6%), macrophages (16.2%) and endothelial cells (14.3%) (Figure 1). IL-6 was expressed mainly by senescent fibroblasts and macrophages while MMP-9 by fibroblasts only (Figure 2). IL-6 positive senescent cells were associated with the extension of vascular wall inflammation (adventitial limited disease vs transmural inflammation: 10.02% vs 4.37% respectively, p< 0.0001) (Figure 3). Giant cell arteritis but not PMR artery culture supernatant induced IL-6-associated senescence that was partially inhibited by IL-6 blockade.
Conclusion: Senescent cells with inflammatory phenotype are present in GCA arteries and are associated with the inflammatory burden of the vascular wall. These findings suggest a potential implication of senescent cells in disease pathogenesis by perpetuating inflammation and affecting vascular remodeling via IL-6 dependent mechanisms.
To cite this abstract in AMA style:
Veroutis D, Argryropouou O, Goules A, Kambas K, Palamidas D, Evangelou K, Havaki S, Polyzou A, Xingi E, Karatza E, Boki K, cavazza a, Kittas C, Thanos D, Ricordi c, marvisi c, Muratore F, Galli E, Croci S, Salvarani C, Gorgoulis V, Tzioufas A. Characterization of Senescent Cells in Temporal Arteries of Patients with Giant Cell Arteritis Reveal an Inflammatory Phenotype and Strong Dependence from IL-6 [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/characterization-of-senescent-cells-in-temporal-arteries-of-patients-with-giant-cell-arteritis-reveal-an-inflammatory-phenotype-and-strong-dependence-from-il-6/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-senescent-cells-in-temporal-arteries-of-patients-with-giant-cell-arteritis-reveal-an-inflammatory-phenotype-and-strong-dependence-from-il-6/