Author/Editor		Bolha, Luka; Pižem, Jože; Frank Bertoncelj, Mojca; Hočevar, Alojzija; Tomšič, Matija; Jurčić, Vesna
Title		Identification of microRNAs and their target genenetworks implicated in arterial wall remodelling ingiant cell arteritis
Type		članek
Publication year		2020
Volume		str. str.
ISSN		1462-0324 - Rheumatology (Oxford, England)
Language		eng
Abstract		Objectives.To identify dysregulated microRNAs (miRNAs) and their gene targets in temporal arteries from GCApatients, and determine their association with GCA pathogenesis and related arterial wall remodelling.Methods.We included 93 formalin-fixed, paraffin-embedded temporal artery biopsies (TABs) from treatment-naive patients: 54 positive and 17 negative TABs from clinically proven GCA patients, and 22 negative TABs from non-GCA patients. miRNA expression analysis was performed with miRCURY LNA miRNome Human PCR Panels andquantitative real-time PCR. miRNA target gene prediction and pathway enrichment analysis was performed usingthe miRDB and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases, respectively.Results.Dysregulation of 356 miRNAs was determined in TAB-positive GCA arteries, among which 78 were sig-nificantly under-expressed and 22 significantly overexpressed above 2-fold, when compared with non-GCA controls. Specifically, TAB-positive GCA arteries were characterized by a significant overexpression of 'pro-synthetic' (miR-21-3p/-21-5p/-146a-5p/-146b-5p/-424-5p) and under-expression of 'pro-contractile' (miR-23b-3p/-125a-5p/-143-3p/-143-5p/-145-3p/-145-5p/-195-5p/-365a-3p) vascular smooth muscle cell phenotype-associated regulatorymiRNAs. These miRNAs targeted gene pathways involved in the arterial remodelling and regulation of the immunesystem, and their expression correlated with the extent of intimal hyperplasia in TABs from GCA patients. Notably,the expression of miR-21-3p/-21-5p/-146a-5p/-146b-5p/-365a-3p differentiated between TAB-negative GCA arteriesand non-GCA temporal arteries, revealing these miRNAs as potential biomarkers of GCA.Conclusion.Identification of dysregulated miRNAs involved in the regulation of the vascular smooth muscle cellphenotype and intimal hyperplasia in GCA arterial lesions, and detection of their expression profiles, enables anovel insight into the complexity of GCA pathogenesis and implies their potential utilization as diagnostic and prognostic biomarkers of GCA.
Keywords		giant cell arteritis microRNA arterial wall velikanski celični arteritis mikroRNA arterijska stena