Abstract
OBJECTIVES: Takayasu arteritis (TAK) is a large-vessel vasculitis characterized by chronic vascular inflammation and extracellular matrix (ECM) remodeling. Long non-coding RNAs (lncRNAs) have emerged as epigenetic regulators of inflammatory and structural vascular processes. This study aimed to evaluate whether lncRNA HOTAIR (HOX transcript antisense RNA) expression in peripheral blood mononuclear cells (PBMCs) is associated with circulating mediators involved in ECM turnover in patients with TAK. METHODS: Fifty-three patients with angiographically confirmed TAK and 53 age- and sex-matched healthy controls were recruited. HOTAIR expression in PBMCs was quantified by reverse transcription-quantitative polymerase chain reaction. Serum concentrations of matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinases-1 (TIMP-1), TIMP-3, extracellular matrix metalloproteinase inducer (EMMPRIN)/CD147, and galectin-3 were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls, TAK patients exhibited significantly higher serum levels of MMP-2 (2245 [1929–2646] vs. 1868 [1576–2355] pg/mL; p=0.036), TIMP-1 (2811 [2644–3216] vs. 2588 [2309–2770] pg/mL; p=0.006), and EMMPRIN/CD147 (1494 [1264–2115] vs. 1310 [1132–1655] pg/mL; p=0.035), along with a reduced MMP-9/TIMP-1 ratio (0.88 [0.61–1.28] vs. 1.18 [0.91–1.41]; p=0.006). HOTAIR expression was markedly downregulated in TAK patients (8.05 [2.52–24.54] vs. 36.09 [30.08–43.85] arbitrary units; p=0.006) and was not associated with disease activity. Notably, HOTAIR expression inversely correlated with circulating MMP-2 (Spearman’s rho -0.276) and EMMPRIN/CD147 (Spearman’s rho -0.280) levels. CONCLUSION: TAK displays a circulating proteolytic profile consistent with enhanced ECM turnover and vascular remodeling. The marked downregulation of HOTAIR supports the involvement of epigenetic mechanisms in TAK and suggests a potential association between reduced HOTAIR expression and MMP-mediated vascular injury.