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

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.

• Authors: Dirk M Wuttge, Anting L Carlsen, Gabriel Teku, Marie Wildt, Göran Rådegran, Mauno Vihinen, Niels H H Heegaard, Roger Hesselstrand
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 61 Issue 1 Pg. 309-318 (12 24 2021) ISSN: 1462-0332 [Electronic] England
• PMID: 33784391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Chemical References

• Circulating MicroRNA

Topics

• Aged
• Circulating MicroRNA (blood)
• Female
• Humans
• Middle Aged
• Pulmonary Arterial Hypertension (metabolism)
• Scleroderma, Systemic (metabolism)