Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is marked by persistent blood clots in pulmonary arteries, leading to significant morbidity and mortality. Emerging evidence highlights the role of microRNAs (miRNAs) in pulmonary hypertension, though findings on miRNA expression in CTEPH remain limited and inconsistent. This systematic review evaluates miRNA expression changes in CTEPH and their direction. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we registered our protocol in International Prospective Register of Systematic Reviews (CRD42024524469). We included studies on miRNA expression in CTEPH with comparative or analytical designs, excluding nonhuman studies, interventions, non-English texts, conference abstracts, and editorials. Databases searched included PubMed, EMBASE, Scopus, CENTRAL, and ProQuest. The Quality Assessment of Diagnostic Accuracy Studies-2 tool assessed bias risk, and results were synthesized narratively. Of 313 unique studies, 39 full texts were reviewed, and 9 met inclusion criteria, totaling 235 participants. Blood samples were analysed using quantitative real time polymerase chain reaction. Seven miRNAs (miR-665, miR-3202, miR-382, miR-127, miR-664, miR-376c, miR-30) were uniformly upregulated, while nine (miR-20a-5p13, miR-17-5p, miR-93-5p, miR-22, let-7b, miR-106b-5p, miR-3148, miR-320-a, miR-320b) were downregulated in CTEPH patients. Two upregulated miRNAs (miR-127 and miR-30a) were consistently associated with previous evidence in the mechanism inducing the development of CTEPH, and five downregulated miRNAs (miR-20-a, miR-17-5p, miR-93-5p, let-7b, miR-106b-5p) were associated with a protective effect against CTEPH. We also identified gaps in the literature where the evidence for five upregulated miRNAs (miR-665, miR-3202, miR-382, miR-664 and miR-376c) and four downregulated miRNAs (miR-22, miR-3148, miR-320-a, and miR-320b) in CTEPH is conflicting. Our findings offer insights into the role of miRNAs in CTEPH and underscore the need for further research to validate these miRNAs as biomarkers or therapeutic targets.