MicroRNA Expression Analysis in Chronic Thromboembolic Pulmonary Hypertension Using Pulmonary Endarterectomy Derived Samples

Abstract

<h3>Purpose</h3> Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare, chronic, debilitating disease characterized by pathological changes that obstruct both sides of the pulmonary arteries (PA). Pulmonary endarterectomy (PEA) can cure the disease, but not all patients qualify for this operation. Aiming to understand a possible contribution of microRNA expression to the thus far poorly understand CTEPH pathophysiology, we here analysed the expression of two candidate microRNAs in PEA specimens. <h3>Methods</h3> MicroRNA specific RT-qPCR for miR-939 and miR-942 was done on RNA from PEA specimens of 46 CTEPH patients and from PAs resected from explant lungs of 10 transplant recipients (predominantly due to COPD, including n = 4 with PH). Associations between microRNA expression and clinical presentation (not all factors available for every patient) were assessed by Spearman correlation. MicroRNA expression between CTEPH and reference PAs was compared by Mann Witney test. <h3>Results</h3> Left-side PEA-derived tissues correlated positively with mPAP and miR-939 (n = 42, R = 0.33, p=0.032) Fig. 1A and miR-942 (n = 43, R = 0.31, p=0.045) Fig. 1B expression levels, while the oxygen saturation (SpO₂) at peak 6-minute walk distance correlated negatively with miR-939 (n = 38, R=-0.41, p=0.009) Fig. 1C. Both microRNAs were elevated in CTEPH, compared to reference PAs, reaching significance for miR-939 mean expression (n = 46 CTEPH vs n = 10 Reference, p=0.0035) and on the left-side samples (n = 44 CTEPH vs n = 8 Reference, p=0.0052), Fig. 1D. <h3>Conclusion</h3> These results suggest that miRNAs may be associated with clinical presentation of CTEPH. Furthermore, the significant elevation compared to reference PA tissue suggest that microRNA dysregulation might be involved in CTEPH pathophysiological mechanisms, associated to endothelial and inflammatory processes encouraging us to investigate further.