Right ventricular (RV) failure prevails as one of the most significant causes of death in patients with pulmonary arterial hypertension (PAH). A study recently published in Cells suggests that alternations in microRNA-21 (miR-21) levels, depending on the situation, may regulate RV dysfunction in PAH. 

In this study, Chang and colleagues established the mechanism of miR-21 in the early and late phases of PAH-induced RV dysfunction, which relate to compensated and decompensated phases, respectively. 

The authors created a rat model of PAH by performing aortovenous fistula surgery. In addition, to simulate the PAH microenvironment, they treated cardiomyocytes with flow-mediated shear stress in 6 dyne for 3 and 8 hours. Echocardiography was performed every 7 weeks after surgery. 


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The expression of miR-21 varied, with an initial increase with RV hypertrophy and a subsequent decrease with RV dysfunction. Similarly, there was an increase in miR-21 levels in cardiomyocytes undergoing shear stress at 3 hours and a decrease at 6 hours. The downregulation of miR-21 was linked to apoptosis; conversely, the overexpression of miR-21 rescued the cardiomyocytes.

When examining the marker in humans, the authors expressed, “Hereby, starting from a clinical observation, we found that despite an increasing expression of circulating miR-21 in patients with PAH, there was a significant drop in circulating miR-21 expression along with RV dysfunction among patients who were hospitalized for decompensated [heart failure].”

Accordingly, the authors prospectively collected data from 2015 to 2020 of patients with heart failure induced by PAH (including atrial and ventricular septal defects), diagnosed according to the European Society of Cardiology /European Respiratory Society guidelines, and controls with similar demographic characteristics. They then evaluated miR-21 as a possible biomarker by assessing serum from patients with PAH-related congenital heart disease (CHD). 

The primary endpoint for CHD due to PAH was hospitalization for heart failure. Of the 76 patients, 19 required hospitalization, and they expressed significantly lower serum miR-21 levels.

“Collectively, our study revealed that the upregulation of miR-21 in the early phase (RV hypertrophy) and downregulation in the late phase (RV dysfunction) under PAH triggered a biphasic regulation of cardiac remodeling and cardiomyocyte apoptosis,” the authors concluded. 

Reference

Chang WT, Wu CC, Lin YW, et al. Dynamic changes in miR-21 regulate right ventricular dysfunction in congenital heart disease-related pulmonary arterial hypertensionCells. 2022;11(3):564. doi:10.3390/cells11030564