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Mechanical stretch induced transcriptomic profiles in cardiac myocytes II

ABSTRACT: The effect of cyclic mecanical stretch on cardiac gene expression was studied in neonatal rat ventricular myocytes (NRVMs).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE107551 | GEO | 2018/03/17

REPOSITORIES: GEO

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Mechanical stretch induced transcriptomic profiles in cardiac myocytes [24-48 hours]

Project description:The effect of cyclic mecanical stretch on cardiac microRNA expression was studied in neonatal rat ventricular myocytes (NRVMs).

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Project description:The effect of cyclic mecanical stretch on cardiac microRNA expression was studied in neonatal rat ventricular myocytes (NRVMs).

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Mechanical stretch induced transcriptomic profiles in cardiac myocytes II

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The ion channel Trpc6a regulates the cardiomyocyte regenerative response to mechanical stretch

Project description:Myocardial damage caused for example by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium. We therefore hypothesized that in adult zebrafish, changes in mechanical loading due to myocardial damage may act as a trigger to induce cardiac regeneration. Based, on this notion we sought to identify mechanosensors which could be involved in detecting changes in mechanical loading and triggering regeneration. Here we show using a combination of knockout animals, RNAseq and in vitro assays that the mechanosensitive ion channel Trpc6a is required by cardiomyocytes for successful cardiac regeneration in adult zebrafish. Furthermore, using a cyclic cell stretch assay, we have determined that Trpc6a induces the expression of components of the AP1 transcription complex in response to mechanical stretch. Our data highlights how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.

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Cardiac Stretch-Induced Transcriptomic Changes are Axis-Dependent

Project description:The goal of this study was to examine the effect of the major axis of biaxial mechanical stretch on cardiac myocyte gene expression and to identify the signaling pathways and transcription factors regulating these changes. Neonatal cardiac myocytes were cultured on a micropatterned substrate, and the primary stretch axis was applied either parallel or transverse to the myofibril direction. RNA sequencing was conducted to study whole genomic expression changes after acute cardiac myocyte stretch. The results showed a more robust gene response to longitudinal than to transverse stretch. After 30 minutes of stretch, 53 and 168 genes were considered differentially expressed (DE) from transverse and longitudinal stretch, respectively. After 4 hours, the number of DE genes increased to 795 in longitudinal stretch while it decreased to 35 in transverse stretch. Gene ontology term (GO) analysis indicated enrichment of TF activity and protein kinase activity by both stretch axes; whereas longitudinal but not transverse stretch caused expression of genes involved in sarcomere organization and cytoskeletal protein binding.

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