Sudden infant death syndrome (SIDS) remains one of the most common and poorly understood diagnoses of death in infants. In this study, we searched for novel biomarkers to aid in elucidating the pathogenesis of SIDS through a bioinformatics analysis of serum-derived extracellular vesicle (EV) miRNAs using next-generation sequencing. Comparative analyses between infants who died of SIDS and those who died from known causes showed that 15 and 38 miRNAs were significantly up- or down-regulated more than twofold in SIDS, respectively. Myocardial-specific miRNAs, such as miR-1, miR-208, and miR-499, which are known to leak from injured heart, were up-regulated markedly in SIDS EVs. Gene target prediction analyses suggested that the MAP signaling pathway, cardiomyocytes, and cardiac ion channels are involved in the pathogenesis of SIDS. Gene ontology analyses revealed that protein phosphorylation, the actin cytoskeleton and myosin complex, and kinase activity are heavily involved in SIDS. Our results indicate that EV myocardial-specific miRNAs are released into the blood from the heart in SIDS, suggesting the pathogenesis of SIDS is associated with cardiac injury. Studies of EV miRNAs using minimally invasive fluid samples could lead to the discovery of new diagnostic markers for SIDS.
Kanno et al. (Tue,) studied this question.