PO-02-142 MIRNA DOWN-REGULATE HYPERTROPHY AND INFLAMMATORY PATHWAYS IN THE TRANSCRIPTOME OF HYPERTROPHIC CARDIOMYOPATHY MYECTOMY TISSUE

Hypertrophic cardiomyopathy (HCM), characterized by asymmetric left ventricular hypertrophy, can lead to severe arrhythmias and sudden cardiac death. The mechanism underlying hypertrophy in HCM has not been fully elucidated. We recently showed that the messenger RNA (mRNA) transcriptome derived from myectomy tissue is gene expression reprogramming predominant transcriptional down-regulation of hypertrophic pro-inflammatory pathways. These changes may represent counter-regulatory efforts prevent unbridled hypertrophy. Herein, we sought determine micro-RNA (miRNA)-omics regulating observed HCM. performed both mRNA- miRNA- sequencing on flash frozen 97 patients with [44 female (45%); mean age at surgery 47 ± 18 years] 23 ostensibly healthy, donor controls [10 (43%); death 43 12 identify miRNA regulators transcriptome. Ingenuity Pathway Analysis was used integrate mRNA datasets perform pathway analyses. Overall, there were 46 differentially expressed (DEmiRNA; 15%) between controls, (93%) which regulate mRNA. Integrating 1246 transcripts DEmiRNA identified 1479 mRNA-miRNA interactions. Of these, 731 interactions across 475 (38%) an inverse relationship indicating a regulatory role for miRNA. miRNA-mediated, alterations impacted 162 crucial pathways, including several inflammatory pathways (e.g., phagosome formation [z-score = -4.2], IL-6 signaling -2.7], acute phase response -2.7]) (cardiac enhanced -2.6], ERK/MAPK -2.3] ERK5 -1.6] signaling). Bottom-up analysis using 15 as most important contributors changes. widespread dysregulation. Almost 40% seen be explained activity Further studies are needed see if early modulation one or more implicated miRNAs able attenuate disease progression