Current state of epigenetics in giant cell arteritis: Focus on microRNA dysregulation

Abstract

Giant cell arteritis (GCA) is a primary systemic vasculitis affecting the elderly, characterized by a granulomatous vessel wall inflammation of large- and medium-sized arteries. The immunopathology of GCA is complex, involving both the innate and adaptive arms of the immune system, where a maladaptive inflammatory-driven vascular repair process ultimately results in vessel wall thickening, intramural vascular smooth muscle cell proliferation, neovascularization and vessel lumen occlusion, which can lead to serious ischemic complications such as visual loss and ischemic stroke. Over the past decade, microRNA (miRNA) dysregulation has been highlighted as an important contributing factor underlying the pathogenesis of GCA. Since current understanding of miRNA involvement in GCA remains largely based on extrapolation of previously determined miRNA functions in vitro or in loss- or gain-of-function studies, an overall insight into the role of miRNA alteration in GCA pathophysiology remains limited. In this narrative review, we summarize the current knowledge on aberrantly expressed miRNAs in GCA and thoroughly discuss the impact of their altered regulatory role in the context of GCA setting. Furthermore, we address challenges and future perspectives in utilization of miRNA-based diagnostic and prognostic biomarkers of GCA in clinical settings.