Abstract

Background MicroRNAs (miRNAs) play an important role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the potential correlation between miRNA expression and the severity of CTEPH remains unclear. Our previous study indicated that miRNAs hsa-let-7b-3p, hsa-miR-17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p are closely involved in CTEPH. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients. Methods A total of eight CTEPH patients and eight healthy adults as a reference group were included, and clinical data including total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), uric acid (UA), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected. Right heart catheterization was conducted to obtain hemodynamic data including cardiac index (CI). The expression levels of let-7b-3p, miR-17-5p, miR-106b-5p, miR-3202, miR-665, and miR-93-5p were measured by quantitative real-time PCR (qPCR). Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients. Results Serum TP and Alb levels were decreased, while LDH, HBDH, and UA levels were increased in CTEPH patients compared with the reference group (P < 0.05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group (P < 0.05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with CI (P < 0.05). Moreover, let-7b-3p tended to be positively correlated with mean pulmonary arterial pressure. Conclusions miR-93-5p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH.

Highlights

  • Chronic thromboembolic pulmonary hypertension (CTEPH), which manifests as progressive exertional dyspnea and right ventricular failure, is caused by pulmonary artery (PA) and pulmonary arteriole obstruction with proximal thromboembolism or distal vascular remodeling [1, 2]

  • Serum total protein (TP) and Alb levels were decreased, while lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and uric acid (UA) levels were increased in chronic thromboembolic pulmonary hypertension (CTEPH) patients compared with the reference group (P < 0:05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group (P < 0:05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with cardiac index (CI) (P < 0:05)

  • CTEPH was defined by the following: (1) a mean pulmonary arterial pressure ðmPAPÞ ≥ 25 mmHg and a pulmonary arterial wedge pressure ðPAWPÞ ≤ 15 mmHg verified by right heart catheterization (RHC) and (2) chronic thrombosis with mismatched perfusion defects demonstrated by computed tomographic angiography or ventilation/perfusion scanning

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Summary

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH), which manifests as progressive exertional dyspnea and right ventricular failure, is caused by pulmonary artery (PA) and pulmonary arteriole obstruction with proximal thromboembolism or distal vascular remodeling [1, 2]. MiRNAs have recently been identified as diagnostic and prognostic biomarkers for cardiovascular diseases including pulmonary hypertension (PH) [8]. We identified several critical miRNAs involved in the progression of CTEPH, including hsa-let-7b-3p, hsa-miR17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p [13], indicating that these miRNAs might be useful in the diagnosis and treatment of CTEPH. Research to date indicates that miRNAs may be correlated with clinical parameters reflecting disease severity in CTEPH patients and may serve as potential prognostic biomarkers. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients. Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients. Conclusions. miR-935p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH

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