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Multi-Omics Characterization of a Human Stem Cell-Based Model of Cardiac Hypertrophy
University of Skövde, Systems Biology Research Environment. University of Skövde, School of Bioscience. Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden. (Translational Bioinformatics)ORCID iD: 0000-0002-5134-4749
University of Skövde, Systems Biology Research Environment. University of Skövde, School of Bioscience. (Translational Bioinformatics)ORCID iD: 0000-0001-9242-4852
BioPharmaceuticals R&D Cell Therapy, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D AstraZeneca, Gothenburg, Sweden. (Translational Bioinformatics)
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2022 (English)In: Life, E-ISSN 2075-1729, Vol. 12, no 2, article id 293Article in journal (Refereed) Published
Abstract [en]

Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. 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 using a multi-omics approach. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48, and 72 h, and their transcriptome and secreted proteome were analyzed. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling. An integrated transcriptome–secretome analysis enabled the identification of multimodal biomarkers that may prove highly relevant for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on both transcriptomic- and secreted-proteomic levels. The results also shed novel insights into the underlying mechanisms of cardiac hypertrophy, and novel putative early cardiac hypertrophy biomarkers have been identified that warrant further investigation to assess their potential clinical relevance.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 12, no 2, article id 293
Keywords [en]
cardiac hypertrophy, cardiomyocytes, disease model, endothelin-1, stem cells, transcriptomics, proteomics
National Category
Cell Biology
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-20931DOI: 10.3390/life12020293ISI: 000763058200001PubMedID: 35207580Scopus ID: 2-s2.0-85125071986OAI: oai:DiVA.org:his-20931DiVA, id: diva2:1639624
Funder
Knowledge Foundation, 20160294Knowledge Foundation, 20160330AstraZeneca
Note

CC BY 4.0

Correspondence: markus.johansson@his.se

This article belongs to the Special Issue The Molecular Mechanism of Cardiovascular Disease

This research was funded by the Systems Biology Research Centre at the University of Skövde under grants from the Knowledge Foundation (20160294, 20160330), Takara Bio Europe, Gothenburg, Sweden, and AstraZeneca R&D, Gothenburg.

Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2023-02-21Bibliographically approved

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Johansson, MarkusUlfenborg, BenjaminHeydarkhan-Hagvall, SepidehSartipy, PeterSynnergren, Jane

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