Dual Roles of Plasma miRNAs in Myocardial Injuries After Polytrauma: miR-122-5p and miR-885-5p Reflect Inflammatory Response, While miR-499a-5p and miR-194-5p Contribute to Cardiomyocyte Damage

Abstract

Cardiac injury after severe trauma is associated with higher mortality in polytrauma patients. Recent evidence suggests that miRNAs play a key role in cardiac pathophysiology and could serve as potential markers of cardiac damage after polytrauma. To explore this hypothesis, plasma miRNA profiles from polytrauma patients (ISS ≥ 16) with and without cardiac injury, stratified by troponin T levels (TnT, > 50 pg/mL vs. < 12 pg/mL), were analysed using NGS and validated via RT-qPCR. Five miRNAs (miR-122-5p, miR-424-5p, miR-885-5p, miR-194-5p, and miR-499a-5p) were found to be significantly upregulated in polytrauma patients with elevated TnT levels. miR-122-5p was associated with markers of right ventricular dysfunction (TAPSE) and left ventricular hypertrophy (IVS/LVPW), while miR-885-5p correlated with left ventricular hypertrophy (IVS/LVPW) and diastolic dysfunction (E/E’ ratio). In vitro, miR-194-5p mimic and miR-499a-5p mimic exhibited more active roles in cardiomyocyte injury by increasing caspase-3/7 activity and/or enhancing caspase-1 activity. Notably, the miR-194-5p mimic significantly enhanced the cytotoxic effects of the polytrauma cocktail, while miR-499a-5p boosted effects of LPS/nigericin stimulation in cardiomyocytes. Our findings identify miR-122-5p and miR-885-5p as potential biomarkers reflecting the cardiomyocyte response to polytrauma-induced inflammation, while miR-499a-5p and miR-194-5p appear to play a direct role in myocardial injury after polytrauma.

Keywords

• polytrauma
• cardiac damage
• miRNA
• troponin T
• NLRP3
• caspase