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Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension

Wuttge, Dirk M. LU ; Carlsen, Anting L. ; Teku, Gabriel LU ; Wildt, Marie LU ; Rådegran, Göran LU ; Vihinen, Mauno LU orcid ; Heegaard, Niels H.H. and Hesselstrand, Roger LU (2022) In Rheumatology (United Kingdom) 61(1). p.309-318
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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microRNA, NT-pro-Brain Natriuretic Protein, pulmonary arterial hypertension, systemic sclerosis
in
Rheumatology (United Kingdom)
volume
61
issue
1
pages
10 pages
publisher
Oxford University Press
external identifiers
  • pmid:33784391
  • scopus:85125013006
ISSN
1462-0324
DOI
10.1093/rheumatology/keab300
language
English
LU publication?
yes
id
4a32a5fd-2b2f-4c90-a0be-fb7442c11800
date added to LUP
2022-04-27 09:06:20
date last changed
2024-06-16 04:27:23
@article{4a32a5fd-2b2f-4c90-a0be-fb7442c11800,
  abstract     = {{<p>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. </p>}},
  author       = {{Wuttge, Dirk M. and Carlsen, Anting L. and Teku, Gabriel and Wildt, Marie and Rådegran, Göran and Vihinen, Mauno and Heegaard, Niels H.H. and Hesselstrand, Roger}},
  issn         = {{1462-0324}},
  keywords     = {{microRNA; NT-pro-Brain Natriuretic Protein; pulmonary arterial hypertension; systemic sclerosis}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{309--318}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology (United Kingdom)}},
  title        = {{Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keab300}},
  doi          = {{10.1093/rheumatology/keab300}},
  volume       = {{61}},
  year         = {{2022}},
}