Identification of microRNAs and their target gene networks implicated in arterial wall remodelling in giant cell arteritis.
OBJECTIVES
To identify dysregulated microRNAs (miRNAs) and their gene targets in temporal arteries from GCA patients, 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-naïve 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 and quantitative real-time PCR. miRNA target gene prediction and pathway enrichment analysis was performed using the 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 significantly 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 regulatory miRNAs. These miRNAs targeted gene pathways involved in the arterial remodelling and regulation of the immune system, 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 arteries and 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 cell phenotype and intimal hyperplasia in GCA arterial lesions, and detection of their expression profiles, enables a novel insight into the complexity of GCA pathogenesis and implies their potential utilization as diagnostic and prognostic biomarkers of GCA.
['Bolha|Luka|L|', 'Pižem|Jože|J|', 'Frank-Bertoncelj|Mojca|M|', 'Hočevar|Alojzija|A|', 'Tomšič|Matija|M|', 'Jurčić|Vesna|V|']
D000368:Aged D000369:Aged, 80 and over D016022:Case-Control Studies D005260:Female D053263:Gene Regulatory Networks D013700:Giant Cell Arteritis D006801:Humans D006965:Hyperplasia D008297:Male D035683:MicroRNAs D008875:Middle Aged D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D010641:Phenotype D013699:Temporal Arteries D017539:Tunica Intima D066253:Vascular Remodeling
microRNA giant cell arteritis temporal artery biopsy vascular remodelling