Chronic Contractile Dysfunction without Hypertrophy Does Not Provoke a Compensatory Transcriptional Response in Mouse Hearts.

ABSTRACT: Diseased myocardium from humans and experimental animal models shows heightened expression and activity of a specific subtype of phospholipase C (PLC), the splice variant PLC?1b. Previous studies from our group showed that increasing PLC?1b expression in adult mouse hearts by viral transduction was sufficient to cause sustained contractile dysfunction of rapid onset, which was maintained indefinitely in the absence of other pathological changes in the myocardium. We hypothesized that impaired contractility alone would be sufficient to induce a compensatory transcriptional response. Unbiased, comprehensive mRNA-sequencing was performed on 6 biological replicates of rAAV6-treated blank, PLC?1b and PLC?1a (closely related but inactive splice variant) hearts 8 weeks after injection, when reduced contractility was manifest in PLC?1b hearts without evidence of induced hypertrophy. Expression of PLC?1b resulted in expression changes in only 9 genes at FDR<0.1 when compared with control and these genes appeared unrelated to contractility. Importantly, PLC?1a caused similar mild expression changes to PLC?1b, despite a complete lack of effect of this isoform on cardiac contractility. We conclude that contractile depression caused by PLC?1b activation is largely independent of changes in the transcriptome, and thus that lowered contractility is not sufficient in itself to provoke measurable transcriptomic alterations. In addition, our data stress the importance of a stringent control group to filter out transcriptional changes unrelated to cardiac function.

SUBMITTER: Matkovich SJ 

PROVIDER: S-EPMC4928941 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature