MicroRNA-21 is Associated with the Severity of Right Ventricular Dysfunction in Patients with Hypoxia-Induced Pulmonary Hypertension

The outcome of pulmonary hypertension (PH) mainly depends on the development of right ventricular (RV) dysfunction, and survival among patients with different etiologies of PH varies. Chronic hypoxia is a major cause of secondary PH, however the mechanisms of its associated RV dysfunction are largely unknown. Herein, we studied the role of microRNA-21 (miR-21) in hypoxia-induced RV dysfunction.

In this longitudinal, prospective study, we enrolled 41 patients with hypoxia-induced PH. Echocardiography was conducted and circulating miR-21 was measured. The expression of miR-21 was also evaluated in hypoxia-treated human pulmonary microvascular endothelial cells (HPECs) and conditioned media. Through the over-expression of miR-21 in H9C2 cells, we further identified crosstalk between the pulmonary circulation and RV.

Among the studied patients, 10 developed RV dysfunction. Notably, the expression of circulating miR-21 was correlated with the severity of RV dysfunction. Likewise, miR-21 was up-regulated in the hypoxia-treated HPECs and its conditioned media in a time-dependent manner. I addition, hypertrophic changes were observed in the hypoxia-treated HPECs. The up-regulation of heart failure-associated markers in H9C2 cells over-expressing miR-21 implied the influence of pulmonary circulatory miR-21 on RV function.

The expression of systemic and pulmonary miR-21 is associated with the severity of RV dysfunction in patients with hypoxia-induced PH.