Danielson, Kirsty M.Shah, RaviYeri, AshishLiu, XiaojunCamacho Garcia, FernandoSilverman, MichaelTanriverdi, KahramanDas, AvashXiao, ChunyangJerosch-Herold, MichaelHeydari, BobakAbbasi, SiddiqueVan Keuren-Jensen, KendallFreedman, Jane E.Wang, Yaoyu E.Rosenzweig, AnthonyKwong, RaymondDas, Saumya2018-07-252018Danielson, K. M., R. Shah, A. Yeri, X. Liu, F. Camacho Garcia, M. Silverman, K. Tanriverdi, et al. 2018. “Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction.” EBioMedicine 32 (1): 172-181. doi:10.1016/j.ebiom.2018.05.013. http://dx.doi.org/10.1016/j.ebiom.2018.05.013.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37298396Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with “beneficial” (decrease LVESVI ≥ 20%, n = 11) and “adverse” (increase LVESVI ≥ 15%, n = 11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n = 331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm.en-USLeft ventricular remodelingMyocardial infarctionmicroRNAExtracellular RNACardiac magnetic resonance imagingRNA sequencingAnd inflammationJournal Article2018-07-2510.1016/j.ebiom.2018.05.013