Altered Plasma Levels and Tissue Expression of Fibroblast Activation Protein Alpha in Giant Cell Arteritis

IF 3.7 2区医学 Q1 RHEUMATOLOGY Arthritis Care & Research Pub Date : 2024-04-29 DOI:10.1002/acr.25354

Shuang Xu, William F. Jiemy, Annemieke M. H. Boots, Suzanne Arends, Yannick van Sleen, Pieter H. Nienhuis, Kornelis S. M. van der Geest, Peter Heeringa, Elisabeth Brouwer, Maria Sandovici

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Abstract

Objective

Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium- and large-sized arteries accompanied by remodeling of the vessel wall. Fibroblast activation protein alpha (FAP) is a serine protease that promotes both inflammation and fibrosis. Here, we investigated the plasma levels and vascular expression of FAP in GCA.

Methods

Plasma FAP levels were measured with enzyme-linked immunosorbent assay in treatment-naive patients with GCA (n = 60) and polymyalgia rheumatica (PMR) (n = 63) compared with age- and sex-matched healthy controls (HCs) (n = 42) and during follow-up, including treatment-free remission (TFR). Inflamed temporal artery biopsies (TABs) of patients with GCA (n = 9), noninflamed TABs (n = 14), and aorta samples from GCA-related (n = 9) and atherosclerosis-related aneurysm (n = 11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts (CD90), macrophages (CD68/CD206/folate receptor beta), vascular smooth muscle cells (desmin), myofibroblasts (α-smooth muscle actin), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9).

Results

Baseline plasma FAP levels were significantly lower in patients with GCA compared with patients with PMR and HCs and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months on remission in patients with GCA and gradually increased to the level of HCs in TFR. FAP expression was increased in inflamed TABs and aorta of patients with GCA compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Some of the FAP⁺ fibroblasts expressed IL-6 and MMP-9.

Conclusion

FAP expression in GCA is clearly modulated both in plasma and in vessels. FAP may be involved in the inflammatory and remodeling processes in GCA and have utility as a target for imaging and therapeutic intervention.

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巨细胞动脉炎患者血浆中成纤维细胞活化蛋白 alpha 的水平和组织表达发生变化

目标巨细胞动脉炎（GCA）的特点是大中型动脉肉芽肿性炎症，并伴有血管壁重塑。成纤维细胞活化蛋白α（FAP）是一种丝氨酸蛋白酶，可促进炎症和纤维化。方法在未经治疗的 GCA（60 人）和多发性风湿病（PMR，63 人）患者（与年龄和性别匹配的健康对照组（HC，42 人）相比）和随访期间（包括无治疗缓解期（TFR）），用酶联免疫吸附法测定血浆 FAP 水平。采用免疫组化方法对 GCA 患者的发炎颞动脉活检组织（9 例）、非发炎颞动脉活检组织（14 例）、GCA 主动脉样本（9 例）和动脉粥样硬化相关动脉瘤样本（11 例）进行 FAP 染色。结果与 PMR 患者和 HC 相比，GCA 患者的血浆 FAP 水平明显较低，且与全身炎症和血管生成指标呈反比。GCA患者病情缓解后3个月，FAP水平进一步下降，而TFR患者的FAP水平则逐渐上升至HC的水平。与对照组组织相比，GCA 患者发炎的 TAB 和主动脉中 FAP 表达增加。FAP 在成纤维细胞和巨噬细胞中大量表达。部分 FAP+ 成纤维细胞表达 IL-6 和 MMP-9。FAP可能参与了GCA的炎症和重塑过程，可作为成像和治疗干预的靶点。

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来源期刊

Arthritis Care & Research RHEUMATOLOGY-

CiteScore

9.40

自引率

6.40%

发文量

368

审稿时长

3-6 weeks

期刊介绍： Arthritis Care & Research, an official journal of the American College of Rheumatology and the Association of Rheumatology Health Professionals (a division of the College), is a peer-reviewed publication that publishes original research, review articles, and editorials that promote excellence in the clinical practice of rheumatology. Relevant to the care of individuals with rheumatic diseases, major topics are evidence-based practice studies, clinical problems, practice guidelines, educational, social, and public health issues, health economics, health care policy, and future trends in rheumatology practice.