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Wuttge DM, Carlsen AL, Teku G, et al. Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension. Rheumatology (Oxford). 2021;61(1):309-318doi: 10.1093/rheumatology/keab300.
Wuttge, D. M., Carlsen, A. L., Teku, G., Wildt, M., Rådegran, G., Vihinen, M., Heegaard, N. H. H., & Hesselstrand, R. (2021). Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension. Rheumatology (Oxford, England), 61(1), 309-318. https://doi.org/10.1093/rheumatology/keab300
Wuttge, Dirk M, et al. "Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension." Rheumatology (Oxford, England) vol. 61,1 (2021): 309-318. doi: https://doi.org/10.1093/rheumatology/keab300
Wuttge DM, Carlsen AL, Teku G, Wildt M, Rådegran G, Vihinen M, Heegaard NHH, Hesselstrand R. Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension. Rheumatology (Oxford). 2021 Dec 24;61(1):309-318. doi: 10.1093/rheumatology/keab300. PMID: 33784391.
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Rheumatology (Oxford). 2021 Dec 24;61(1):309-318. doi: 10.1093/rheumatology/keab300.

Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension.

Rheumatology (Oxford, England)

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

Affiliations

  1. Department of Clinical Sciences Lund, Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
  2. Department of Autoimmunology & Biomarkers, Statens Serum Institute, Copenhagen S, Denmark.
  3. Department of Experimental Medical Science, Protein Structure Bioinformatics, Lund, Sweden.
  4. Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden.
  5. The Hemodynamic Lab, the Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine, Skåne University Hospital, Lund, Sweden.
  6. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
  7. Institute of Clinical Research, Clinical Biochemistry, University of Southern Denmark, Odense, Denmark.

PMID: 33784391 DOI: 10.1093/rheumatology/keab300

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.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Keywords: NT-pro-Brain Natriuretic Protein; microRNA; pulmonary arterial hypertension; systemic sclerosis

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