THU0006 ASSOCIATION BETWEEN ALTERED MICRORNA EXPRESSION AND ARTERIAL WALL REMODELING IN GIANT CELL ARTERITIS

Background: Immunopathology of giant cell arteritis (GCA) results from dysregulated interactions between arterial wall-resident non-immune cells, e.g. vascular smooth muscle cells (VSMCs), and components of the immune system [1]. In spite of several efforts at identifying microRNAs (miRNAs) implicated in the pathogenesis of GCA, the overall information on miRNA involvement in GCA and its related arterial fibro-sclerotic alterations remains scarce. Objectives: To analyze miRNA expression and identify target genes of dysregulated miRNAs in temporal arteries from GCA patients, and to determine their association with GCA-associated arterial wall remodeling. Methods: The study included formalin-fixed, paraffin-embedded temporal artery biopsies (TABs) from 71 clinically diagnosed treatment-naive patients fulfilling the ACR 1990 classification criteria, and 22 non-GCA subjects (control group). Of GCA patients, 54 histologically positive and 17 histologically negative TABs were included. miRNA expression profiling was performed with quantitative real-time PCR (qPCR)-based miRNA PCR panels and qPCR. The miRDB database and STRING protein-protein network analysis were used for identification of miRNA gene targets and their pathway enrichment analysis, respectively. Results: Of 356 detected miRNAs, we determined significant under-expression of 78 and significant over-expression of 22 miRNAs (≥ 2-fold; p Conclusion: Our study demonstrated an extensive dysregulation of arterial miRNA networks in GCA, favoring the pathogenic switch in the VSMC phenotype and associated intimal hyperplasia. We identified several miRNAs, which could represent potential novel GCA biomarkers. Furthermore, our results imply that the ubiquitin-proteasome system and the RNA silencing complex are targets of dysregulated arterial miRNA networks in GCA lesions, providing new insight into the complexity of GCA pathogenesis. References: [1]Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol 2013;9:731–40. Acknowledgments: This work was supported by the Slovenian Research Agency [research core funding No. P3-0054]. Disclosure of Interests: None declared