Dataset Information

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.

SUBMITTER: Wuttge DM

PROVIDER: S-EPMC8742821 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationalePatients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) continue to have an unacceptably high mortality rate despite the progress achieved with pulmonary arterial vasodilator therapies.ObjectivesWe sought to determine whether SSc-PAH is a clinically distinct pulmonary vascular disease phenotype when compared with idiopathic pulmonary arterial hypertension (IPAH) on the basis of progression of echocardiographic right ventricular (RV) dysfunction.MethodsRetrospective analysis of echocardiographic data in 13 patients with SSc-PAH and 11 patients with IPAH was used to delineate the progression of RV dysfunction during single or combination pulmonary arterial vasodilator therapy. All patients had right heart catheterization-confirmed pulmonary arterial hypertension as well as complete baseline (at the time of diagnosis) and follow-up (most recent) echocardiograms. We excluded patients with significant scleroderma-associated interstitial lung disease. Adjusting for time of follow-up and disease duration, we performed mixed model regression analyses comparing the changes between the two groups for different echocardiographic variables: tricuspid annular plane systolic excursion, tricuspid regurgitation jet velocity, right atrial area, and RV diameter.ResultsThe mean ages for the SSc-PAH and IPAH groups were 60.8 and 48.2 years, respectively. The mean follow-up periods for the two groups were 3.8 and 1.95 years, respectively. Tricuspid annular plane systolic excursion did not improve in patients with SSc-PAH, whereas it increased in the patients with IPAH (-0.38 mm, P?=?0.87; vs. +5.6 mm, P?=?0.02). The other echocardiographic variables showed a trend toward worsening in the SSc-PAH group and improvement in the IPAH group.ConclusionsOur results indicate that, in patients with SSc-PAH, echocardiographic RV function does not improve over time compared with that of patients with IPAH, despite institution of pulmonary artery vasodilator therapies.