Expression of MicroRNAs in Surgical Specimens of Patients with Chronic Thromboembolic Pulmonary Hypertension

Purpose Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease, for which the underlying pathophysiological mechanisms have yet to be fully elucidated. In recent years, microRNAs have emerged as important players in regulation of physiological processes, and dysregulation of microRNA expression has been linked to various diseases. So far, only a limited number of studies has investigated microRNAs in CTEPH. Therefore, the aim of this study was to investigate whether microRNAs are also detectable in tissue specimens obtained from patients undergoing pulmonary endarterectomy (PEA), since differential expression in the tissues could suggest a role of these microRNAs in disease development. Methods Tissue specimens were obtained from patients 16 patients undergoing PEA at the University Hospital Zurich, between 2016 and September 2018. RNA was extracted from FFPE blocks, and expression levels of three microRNAs identified as potential players in CTEPH development through a study of circular RNAs (Miao et al, Medicine 2017), miR-939, miR-942 and miR-92a-2-5p, were measured by microRNA-specific RT-qPCR. In addition, miR-210, the most important microRNA in regulation of hypoxia was measured. Expression of microRNAs was correlated to various clinical factors. Results Of the three miR-candidates measured in plasma before, miR-939 and miR-942 were detectable in PEA tissue specimens. In addition, the hypoxamiR miR-210 was also detectable and represented the microRNA with the highest expression levels. Expression of miR-939 showed a significant negative correlation with peripheral oxygen saturation (p=0.03; Spearman's R=-0.548) and pulmonary vascular resistance (p=0.05, R=-0.502), while miR-942 expression negatively correlated with Jamieson Classification (p=0.04, R=-0.623). Conclusion This pilot study has shown for the first time that microRNAs are readily detectable in material extracted during PEA. Our data shows that microRNAs are differentially expressed between different patients, and that microRNA expression is correlated with various factors of clinical presentation. Thus, our data highlight that microRNA expression warrants further investigation as their dysregulation might be involved in the development of CTEPH.