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MicroRNA expression profiles in a human induced pluripotent stem cell‐derived model of diabetic cardiomyopathy
Author(s) -
Mishra Manoj K.,
Horikoshi Yuichi,
Pan Xiaoqing,
Liu Pengyuan,
Bai Xiaowen,
Bosnjak Zeljko J.,
Kriegel Alison J.,
Liang Mingyu
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.713.2
Subject(s) - diabetic cardiomyopathy , induced pluripotent stem cell , microrna , biology , transcriptome , microbiology and biotechnology , stem cell , cardiomyopathy , cancer research , endocrinology , bioinformatics , medicine , gene expression , genetics , heart failure , gene , embryonic stem cell
Diabetic cardiomyopathy (DCM) is a common and important health concern in the rapidly growing population of diabetic patients. At present, no specific drug treatment exists to prevent diabetes‐induced cardiac dysfunction, a complex multifactorial condition that is distinguished by a unique set of metabolic, structural, and molecular changes within the DCM. The advances in disease modeling using human induced pluripotent stem cells (iPSCs) have opened novel paths to study human physiology and disease at the cellular level. Here, we characterized an in vitro cell based model for DCM developed by exposing human induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs) to a diabetic‐like environment (10 mM glucose, 10 nM human‐endothelin‐1, and 1 mM cortisol). The treated cells exhibited metabolic shift (demonstrated by reduced glucose oxidation and increased fatty acid oxidation) and hypertrophy (demonstrated by hypertrophic morphology and increased expression of hypertrophic markers such as BNP, ANP, ACTA1 and MYH7. MicroRNAs (miRNAs) are key factors in controlling complex regulatory networks in cellular functions and disease processes. We performed a small RNA deep sequencing analysis to identify miRNAs associated with this in vitro DCM model. We identified 57 differentially regulated ( p <0.05) miRNAs (26 up‐ and 31 down‐regulated) in diabetic CMs compared with control iPSC‐CMs (10 mM mannitol). The differential expression of several miRNAs was verified by real‐time PCR. These findings suggest miRNAs might be involved in this model of DCM. Further investigation will be required to examine functional roles for these miRNAs and identify the mechanisms by which these miRNAs might contribute to the development of DCM. Support or Funding Information Supported by NIH Grant P01GM066730. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .