Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension. (30th March 2021)

• Record Type: Journal Article
• Authors: Wuttge, Dirk M; Carlsen, Anting L; Teku, Gabriel; Wildt, Marie; Rådegran, Göran; Vihinen, Mauno; Heegaard, Niels H H; Hesselstrand, Roger
• Is Part Of: Rheumatology. Volume 61:Number 1(2022)
• Page Start: 309
• Page End: 318
• Publication Date: 2021-03-30
• Subjects: systemic sclerosis -- pulmonary arterial hypertension -- microRNA -- NT-pro-Brain Natriuretic Protein; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keab300
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objectives: SSc-associated pulmonary arterial hypertension (SSc-APAH) is a late but devastating complication of SSc. Early identification of SSc-APAH may improve survival. We examined the role of circulating miRNAs in SSc-APAH. Methods: Using quantitative RT-PCR the abundance of mature miRNAs in plasma was determined in 85 female patients with ACA-positive lcSSc. Twenty-two of the patients had SSc-APAH. Sixty-three SSc controls without PAH were matched for disease duration. Forty-six selected miRNA plasma levels were correlated with clinical data. Longitudinal samples were analysed from 14 SSc-APAH and 27 SSc patients. Results: The disease duration was 12 years for the SSc-APAH patients and 12.7 years for the SSc controls. Plasma expression levels of 11 miRNAs were lower in patients with SSc-APAH. Four miRNAs displayed higher plasma levels in SSc-APAH patients compared with SSc controls. There was significant difference between groups for miR-20a-5p and miR-203a-3p when correcting for multiple comparisons ( P = 0.002 for both). Receiver operating characteristics curve showed AUC = 0.69–0.83 for miR-21-5p and miR-20a-5p or their combination. miR-20a-5p and miR-203a-3p correlated inversely with NT-pro-Brain Natriuretic Protein levels (r = −0.42 and −0.47). Mixed effect model analysis could not identify any miRNAs as predictor of PAH development. However, miR-20a-5p plasma levels were lower in the longitudinal samples of SSc-APAH patients than in the SSc controls. Conclusions: Our study links expression levels of the circulating plasma miRNAs, especially miR-20a-5p and miR-203a-3p, to the occurrence of SSc-APAH in female patients with ACA-positive lcSSc.