Abstract P3021: Circulating Exosomal MicroRNAs As Biomarkers For Pulmonary Embolism

Pulmonary Embolism (PE) is the third leading cause of death worldwide. Current treatment for PE, including thrombolytics and anticoagulants, have serious side effects. Protein and RNA biomarkers presently used to diagnose PE do not have the necessary specificity or sensitivity. Therefore, discovery of predictive biomarkers for therapeutic effects and adverse outcomes is imperative. MicroRNAs (miRNAs) are known to regulate gene expression networks and their expression levels reflect the physiological state of their cell of origin. By investigating these circulating miRNAs, we can gain valuable insight into the state of the damaged cells or tissue. Here, we innovated a novel methodology to isolate exosomes from patient platelet-free plasma that provides better yield of both exosomes and their RNA content. We are the first to stratify the PE patient samples according to clinical severity (low-risk, sub-massive, massive PE) and analyze the correlations of the exosomal miRNA biomarkers with PE severity. We found that exosomes from PE patients are more heterogeneous, lower in concentration and larger in size compared to healthy controls. Further, exosomes from PE patient samples pack more RNA than healthy controls. With the results from ongoing miRNA sequencing, we will be able to identify miRNAs and other short non-coding RNAs as potential diagnostic biomarkers that best correlate with PE severity. Validation and predictive studies using qRT-PCR will push the frontiers on circulating small RNA biomarkers in PE and other cardiovascular diseases. Finally, network analysis on the potential RNA biomarkers will provide information for future studies on disease mechanisms and therapeutics development.