Circulating Plasma microRNAs In Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-APAH) is a late but devastating complication of systemic sclerosis (SSc). Early identification of SSc-APAH may improve survival. We examined the role of circulating micro-RNAs (miRNAs) in SSc-APAH.Using quantitative RT-PCR the abundance of mature miRNAs in plasma were determined in 85 female patients with anti-centromere antibody positive limited cutaneous SSc. 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.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-BNP 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.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 anti-centromere antibody positive limited cutaneous SSc.

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Authors: Dirk M Wuttge, Anting L Carlsen, Gabriel Teku, Marie Wildt, Göran Rådegran, Mauno Vihinen, Niels H H Heegaard, Roger Hesselstrand