Altered plasma levels and tissue expression of fibroblast activation protein alpha in giant cell arteritis

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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 which 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 ELISA in treatment-naive GCA (n=60) and polymyalgia rheumatica (PMR, n=63) patients (compared to age- and sex-matched healthy controls (HC), n=42) and during follow-up, including treatment free remission (TFR). Inflamed temporal artery biopsies (TAB) of GCA patients (n=9), non-inflamed TAB (n=14), aorta samples from GCA- (n=9) and atherosclerosis-related aneurysm (n=11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts(CD90), macrophages(CD68/CD206/FRβ), vascular smooth muscle cells(desmin), myofibroblasts(αSMA), interleukin(IL)-6 and matrix metalloproteinase(MMP)-9.

RESULTS: Baseline plasma FAP levels were significantly lower in GCA compared to PMR patients and HC, and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months upon remission in GCA, and gradually increased to the level of HC in TFR. FAP expression was increased in inflamed TAB and aorta of GCA patients compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Part 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 target for imaging and therapeutic intervention.

Original languageEnglish
Number of pages35
JournalArthritis Care & Research
DOIs
Publication statusAccepted/In press - 29-Apr-2024

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