Abstract 11249: Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy
Background: Regarding disease pathogenesis, it has become evident that confinement to analysis of protein-coding regions of the genome is incomplete since many noncoding variants are associated with important human diseases
Objectives: Identification of novel molecular predictive markers for the course of human enterovirus (CVB3) cardiomyopathy, and of noncoding elements in the genome influencing the grossly different antiviral capacity of individual patients.
Methods: Transcriptome mapping of CVB3 cardiomyopathy patients revealed distinctive cardiac microRNA (miR) patterns associated with either spontaneous virus clearance and recovery (CVB3-ELIM), or virus persistence and progressive clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754 miRs in endomyocardial biopsies (EMBs) of test cohorts was performed at their initial presentation, and those spontaneously eliminating the virus were compared to those with virus persistence on follow-up.
Results: Initial miR profiling revealed highly significant differences in the cardiac levels of 16 miRs, but not in protein-coding genes. Eight miRs were strongly induced in CVB3-PERS only (miRs 135b, 155, 190a, 422a, 489, 590, 601, 1290), but undetectable in CVB3-ELIM or controls. Remarkably, four of the miRs deregulated in CVB3-PERS vs. CVB3-ELIM are primate-specific, and thus do not exist in murine models of human CVB3 cardiomyopathy. Further evaluation of this primary distinctive miR pattern in validation cohorts, and multivariate statistical analysis, led to the definition of a secondary simplified predictive miR profile suggested for future clinical use.
Conclusions: A clinical application of these data is cardiac miR profiling to assess the risk of virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy. Patients at risk are eligible for immediate antiviral therapy to minimize irreversible cardiac damage. A basic science aspect is the failure of protein-coding gene profiling to identify significant predictors, suggesting that individual antiviral capacity is strongly influenced and reflected by noncoding miR transcripts some of which may constitute new therapeutic targets.
Author Disclosures: W. Poller: None.
- © 2014 by American Heart Association, Inc.