Abstract 19170: Plasma MicroRNA Sequencing in Subjects With and Without Hypercoagulability
Introduction: Plasma microRNAs (miRs) regulate messenger RNA transcription through complimentary base-pair binding and target gene repression. Increased circulating miRNA has been noted in patients with cardiovascular disease (CVD), but less is known regarding miRNAs associated with hypercoagulability, a risk factor for thrombotic events.
Methods: Our cohort included 22 healthy volunteers (HV) and 20 patients with stable heart failure (HF) with and without hypercoagulability. Using a quantitative nuclease protection assay coupled with next generation sequencing, we sequenced 2,256 miRs annotated in miRBASE v20 on the Illumina platform. The sequence data was standardized and normalized to account for counts below the limit of detection. Differentially regulated miRs were analyzed with the DIANA miRpath and KEGG pathway analysis tools. Hypercoagulability was defined as platelet fibrin clot strength ≥65mm measured by a new point-of-care thrombelastography assay (TEG6s).
Results: We identified 56 miRs targeting 2414 genes and 21 biochemical pathways that were differentially regulated between HV and HF patients with a corrected p-value of < 0.05 and fold-change >±1.5; 1 miR was up-regulated and 55 miRs were down-regulated. miR-339, -4448, and -4633 were down regulated in subjects with hypercoagulability and miR-4485, -6089, -197, 5787, 4284, 6087, 3960, and -762 were upregulated in subjects with normal coagulability (p>0.05 for all). In addition, mir-1286 and mir-6786 were differentially regulated in HV and HF patients (Fig).
Conclusions: We describe differentially regulated miRs in subjects with and without hypercoagulability. MiRs may have a potential biologic role in the regulation of thrombosis. The clinical significance of these findings should be evaluated in a larger cohort with the goal of identifying miRs that mediate thrombotic risk.
Author Disclosures: U.S. Tantry: None. A. Ulynov: None. M. Ahmad: None. K. Bliden: None. P. Shah: None. R. Iyer: None. P.A. Gurbel: Research Grant; Modest; significant. Research Grant; Significant; Haemonetics, Merck, Duke Clinical Research Institute, Harvard Clinical Research Institute, National Institutes of Health, New Haven Pharmaceuticals, Coramed Technologies, MedImmune, and Sinnowa. Honoraria; Modest; modest. Honoraria; Significant; AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo/Lilly, Merck, Janssen Pharmaceuticals, New Haven Pharmaceuticals, Bayer, and Haemonetic. Consultant/Advisory Board; Modest; modest. Consultant/Advisory Board; Significant; AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo/Lilly, Merck, Janssen Pharmaceuticals, New Haven Pharmaceuticals, Bayer, and Haemonetic.
- © 2016 by American Heart Association, Inc.