Plasma exosomal miR-596: a novel biomarker predicts survival in patients with idiopathic pulmonary artery hypertension

Abstract

Objective To determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods The study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction. Results This study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival. Conclusions High levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.

Emerging role of exosomes in vascular diseases

“…Such studies are common and have identified valuable markers through the validation of clinical specimens. For example, low plasma levels of exosomal miR-150 (27) and miR-483 (250) and high levels of miR-596 (251) in patients with PAH suggested a poor prognosis; DQ593039 correlated significantly with diagnostic parameters in patients with CTEPH, and this piRNA showed potential value as a noninvasive screening agent (252). In practice, however, we do not know the donor cells, recipient cells, or specific mechanisms of abnormal exosomes in these disease groups, so further studies may be needed to elucidate the mechanisms of these markers in molecular, cellular, and animal models.…”

miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis

“…Therefore, circulating miRNAs are a useful diagnostic and prognostic biomarker of PAH [ 49 , 50 ]. Previous studies have reported the association of circulating miRNAs, including miR-27b and miR-451 [ 51 ], miR-125a-5p [ 52 ], miR-509-3p [ 53 ], miR-206 [ 54 ], miR-483 [ 55 ], miR-211 [ 56 ], miR-143 [ 57 ], miR-596 [ 58 ], and miR-208-Mef2 [ 59 ] axis with the prognosis of PAH. The miR-29 family members have been reported as anti-fibrotic miRNAs [ 48 ].…”

Recent Advances of Using Exosomes as Diagnostic Markers and Targeting Carriers for Cardiovascular Disease

“…53 miR-596 derived from plasma exosomes can survive in patients with idiopathic pulmonary arterial hypertension, and it is a novel predictive biomarker. 54 High miR-596 levels in idiopathic pulmonary arterial hypertension have been detected, and they might be associated with severity and poor outcome from this condition. 54 The different expressions of exosomal miRNAs can affect pulmonary remodeling and pulmonary arterial pressure.…”