Dataset Information

In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and spezialized regulation

ABSTRACT: Insulin signaling regulates cardiac substrate utilization and is implicated in physiological adapations of the heart. While extensively investigated in several metabolic organs using phosphoproteomic strategies, the signaling response elicited in cardiac tissue in general, and specifically in the spezialized cardiomyocyte cells, has not yet been investigated to the same extend.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Jonathan Achter

LAB HEAD: Alicia Lundby

PROVIDER: PXD050545 | Pride | 2024-08-10

REPOSITORIES: Pride

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Publications

In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.

Achter Jonathan Samuel JS Vega Estefania Torres ET Sorrentino Andrea A Kahnert Konstantin K Galsgaard Katrine Douglas KD Hernandez-Varas Pablo P Wierer Michael M Holst Jens Juul JJ Wojtaszewski Jørgen Frank Pind JFP Mills Robert William RW Kjøbsted Rasmus R Lundby Alicia A

Cardiovascular diabetology 20240718 1

<h4>Background</h4>Insulin signaling regulates cardiac substrate utilization and is implicated in physiological adaptations of the heart. Alterations in the signaling response within the heart are believed to contribute to pathological conditions such as type-2 diabetes and heart failure. While extensively investigated in several metabolic organs using phosphoproteomic strategies, the signaling response elicited in cardiac tissue in general, and specifically in the specialized cardiomyocytes, ha ...[more]

PMID: 39026321

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Project description:Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. Cardiac hypertrophy manifests as an enlargement of the individual cardiomyocytes, which impairs the function of the heart. The only way to cure end-stage cardiac myopathy is by heart transplantation, a possibility limited due to lack of donor hearts. Therefore, early diagnosis of cardiac hypertrophy is needed in order to be able to initiate interventions that may prevent further progression of the disease. The mechanisms underlying the development of cardiac hypertrophy are yet not well understood. To increase the knowledge about mechanisms and regulatory pathways involved in the progression of cardiac hypertrophy, we have developed a human induced pluripotent stem cell (hiPSC)-based in vitro model of cardiac hypertrophy and performed extensive characterization of the model using multi-omics analyses. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48 and 72 hours and their transcriptome and secreted proteome were analyzed thoroughly. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling, actin cytoskeleton signaling and PI3K/AKT signaling. Cluster analysis of the differentially expressed genes showed that there are numerous clusters of genes that are dysregulated over the time period of 8 to 72h. An integrated transcriptome-secretome analysis enabled the identification of multimodal biomarkers of high relevance for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on transcriptomic- and secreted proteomic level. The results also provide novel insight into the underlying mechanisms of cardiac hypertrophy and novel putative early cardiac hypertrophy biomarkers have been identified that will be further validated to assess their clinical relevance.

Dataset Information

In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and spezialized regulation

Publications

In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.

Similar Datasets

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