Circulating miRNA analysis in Pulmonary Arterial Hypertension patients, overexpression of miR-3168 downregulates BMPR2 and impairs angiogenesis in vitro

Pulmonary Arterial Hypertension (PAH) is a rare disease where the thickening of the precapillary pulmonary arteries ends up inducing right heart failure. Nowadays, getting an early diagnosis is complicated and usually delayed until performing right-heart catheterization. In this work, we performed small RNA sequencing in the plasma of idiopathic PAH patients and controls. We were able to find 29 differentially expressed microRNAs and validate 7 of them in a nationwide cohort (let-7a-5p, let-7b-5p, let-7c-5p, let-7f-5p, miR-9-5p, miR-31-5p, miR-3168). We then used classification models to analyze their potential as PAH predictors. In the first half of our cohort, we obtained a model with an AUC of 0.888. Although, this value lowered to 0.738 after using this model in the whole cohort of patients. Also, we validated the effect of miR-3168, a novel upregulated miRNA in PAH patients that targets the BMPR2 and impairs angiogenesis as measured in tube formation assay. In conclusion, we found novel downregulated and upregulated microRNAs in idiopathic PAH patients. We developed a 3-microRNA signature for diagnosis and validated in vitro that miR-3168 targets BMPR2 and impairs angiogenesis. Differential expression analysis between Pulmonary Arterial Hypertension patients and healthy donors matched by age