The following is a summary of “Transpulmonary Expression of Exosomal microRNAs in Idiopathic and Congenital Heart Disease–Related Pulmonary Arterial Hypertension,” published in the November 2023 issue of Cardiology by Chang et al.

Pulmonary arterial hypertension (PAH) is a severe condition marked by intricate pathogenic factors. Recently, exosomes carrying microRNAs (miRs) have emerged as promising biomarkers. These transpulmonary exosomal miRs provide critical insights into the microenvironments within pulmonary circulation. In this study, their objective was to investigate the potential of transpulmonary exosomal miRs in distinguishing between idiopathic PAH and PAH related to congenital heart disease (CHD).

Through right heart catheterization, researchers collected exosomes from pulmonary arteries in 25 patients diagnosed with idiopathic PAH and 20 patients with CHD-related PAH. Employing next-generation sequencing, the investigators identified several candidate exosomal miRs. Using quantitative polymerase chain reaction, they validated the expressions of these miRs. Their findings unveiled significantly elevated expressions of miR-21, miR-139-5p, miR-155-5p, let-7f-5p, miR-328-3p, miR-330-3p, and miR-103a-3p in patients with CHD-related PAH compared to those with idiopathic PAH. Particularly, miR-21 exhibited the highest expression in CHD-related PAH patients. These outcomes were further confirmed in an external cohort comprising 10 idiopathic PAH patients and 8 CHD-related PAH patients. Utilizing an in vitro flow model simulating the shear stress experienced by pulmonary endothelial cells, the study group observed a significant upsurge in miR-21 expression. Additionally, suppressing miR-21 helped alleviate the shear stress-induced reduction of the RAS/phosphatidylinositol 3-kinase/protein kinase B pathway, thereby mitigating apoptosis.

In conclusion, their study unveiled a distinct elevation of transpulmonary exosomal miR-21 expression,  using next-generation sequencing analysisparticularly notable in patients with CHD-related PAH. Further exploration is needed to unravel the regulatory mechanisms involving miR-21 in the pathophysiology of PAH, shedding light on potential therapeutic avenues.

Source: ahajournals.org/doi/10.1161/JAHA.123.031435