Introduction: Perfusion defects after pulmonary embolism (PE) are involved in chronic thromboembolic pulmonary hypertension (CTEPH) development. Physical activity is useful on cardiovascular diseases recover. Aim: To study dysregulated microRNAs (miRNAs) before and after exercise in patients with persistent lung perfusion defects after PE.

Methods: Patients with persistent perfusion defects after PE carried out a cardiopulmonary exercise testing (CPET). Blood samples were drawn before and after exercise and 179 miRNAs were quantified. Logistic regression and mixed linear model were employed to data analysis. Mirwalk database was used to in silico analysis.

Results: Fifteen patients were analyzed. Two miRNAs with higher maximun probability effect (MPE): miR-16-5p and miR-451a (MPE: 78.12 % and 84.23% respectively) were found. A negative association for miR-16-5p and miR-451a and peak oxygen consumption VO2 (peak VO2, mL/kg/min) was observed (p<0.001 and p=0.009 respectively. On the contrary, it was found a positive association between ventilatory equivalent of CO2 at the anaerobic threshold (VE/VCO2 at AT) and miR-16-5p and miR-451a expression (p < 0.001 and p = 0.009 respectively). In silico analysis showed miR-16-5p regulates expression of genes implicated in cell cycle, hypoxia or vascular endothelial growth factor biological pathways.

Conclusions: MicroRNAs expression would be associated with responsiveness to exercise in patients with residual thrombosis after PE. These miRNAs might act by regulating biological pathways involved in CTEPH development. SEPAR (22/1334), ISCIII (PI18//01640), CSYF-0116-2020.