Abstract 263: MYH14 Protects Against of Isoproterenol-induced Left Ventricular Hypertrophy and Fibrosis

Abstract

Objectives: We had previously identified Myh14 as a genetic modifier of isoproterenol-induced left ventricular hypertrophy through a genome-wide association study performed among Hybrid Mouse Diversity Panel strains. Whether left ventricular hypertrophy due to Myh14 deficiency is compensatory or maladaptive is not well established. Moreover, though MYH14 had been previously reported in the intercalated disc of cardiomyocytes, the mechanisms by which Myh14 deficiency leads to left ventricular hypertrophy is unknown. Methods: We performed RNA-seq on cardiac tissues from 12-week old male Myh14 +/+ and -/- mice that had been treated under control versus isoproterenol conditions for 3 weeks. We examined the differentially expressed genes to identify enriched gene ontology (GO) terms altered by Myh14 deficiency at the transcriptional level. Findings: Differential expression analysis showed an enrichment of transcripts coding for extracellular matrix proteins in isoproterenol treated versus control mice, many of which were further enriched in Myh14 -/- versus +/+ mice. Transcripts uniquely differentially expressed due to Myh14 deficiency were enriched for GO terms such as inorganic cation import across plasma membrane, inner ear receptor cell / neuron development, response to purine-containing compound, and sensory perception of mechanical stimulus, supporting the roles these pathways play in mediating the impact of Myh14 deficiency on cardiac remodeling. Conclusions: Our RNA-seq results suggest that MYH14 plays a protective role against mechanical stress. Future directions include elucidation of specific roles that the affected pathways play in mediating mechanical stress as a result by Myh14 deficiency as well as impact on the observed phenotype of left ventricular hypertrophy and fibrosis.