MicroRNA Expression Correlates with Clinical Presentation of Chronic Thromboembolic Pulmonary Hypertension

Abstract

Abstract Background Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare, debilitating disease characterized by pathological changes that obstruct both sides of the pulmonary arteries (PA). The underlying pathophysiology is poorly understood. Aims Trying to understand the possible contribution of microRNAs to CTEPH pathophysiology, we here analysed the expression of four candidate microRNAs in pulmonary endarterectomy (PEA) specimens. Methods MicroRNA specific RT-qPCR for miR-939, miR-942, let-7b and let-7d was done on RNA from PEA specimens of 50 CTEPH patients and from PAs resected from explant lungs of 48 transplant recipients (25 due to COPD, and including 22 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 Whitney test. Results Expression levels in left-side PEA-derived tissues correlated negatively with: CRP for let-7d (n = 49, R = -0.29, p=0.039), oxygen saturation (SpO2) at peak 6-minute walk distance for miR-939 (n = 44, R = -0.39, p=0.007), and Right Jamieson classification for miR-942 (n = 40, R = -0.34, p=0.03). Right-side samples let-7d levels correlated negatively with mPAP (n = 42, R = -0.33, p=0.031). Contrastingly, mean expression levels of miR-942 showed positive correlation with mPAP (n = 49, R = 0.28, p=0.049) and Borg Scale showed a similar tendency with miR-939 (n = 50, R = 0.31, p=0.027). Compared to reference PAs, right-side expression of miR-942 reached significance (n = 47 CTEPH vs n = 46 Reference, p=0.0001). Conclusions Correlations with clinical parameters 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, encouraging us to investigate further.