<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=undefined&type=result"></script>');
-->
</script>

COPY SCRIPT

For further information contact us at helpdesk@openaire.eu

Chronic ethanol exposure induces mitochondrial dysfunction and alters gene expression and metabolism in human cardiac spheroids

descriptionPublicationkeyboard_double_arrow_right Article 17 Feb 2023Publisher:WileyJournal:Alcohol: Clinical and Experimental Research, volume 47, pages 643-658 (issn: 2993-7175, eissn: 2993-7175,

Authors:

Hyun Hwang; Rui Liu; Ronald Eldridge; Xin Hu;

Parvin Forghani; Dean P. Jones;

Chunhui Xu;

doi: 10.1111/acer.15026

pmid: 36799338

pmc: PMC10149610

Chronic ethanol exposure induces mitochondrial dysfunction and alters gene expression and metabolism in human cardiac spheroids

- Summary
- Subjects
- Metrics

Abstract

AbstractBackgroundChronic alcohol consumption in adults can induce various cardiac toxicities such as arrhythmias, cardiomyopathy, and heart failure. Prenatal alcohol exposure can increase the risk of developing congenital heart defects among offspring. Understanding the molecular mechanisms underlying long‐term alcohol exposure‐induced cardiotoxicity can help guide the development of therapeutic strategies.MethodsCardiomyocytes derived from human‐induced pluripotent stem cells (hiPSC‐CMs) were engineered into cardiac spheroids and treated with clinically relevant concentrations of ethanol (17 and 50 mM) for 5 weeks. The cells were then analyzed for changes in mitochondrial features, transcriptomic and metabolomic profiles, and integrated omics outcomes.ResultsFollowing chronic ethanol treatment of hiPSC‐CMs, a decrease in mitochondrial membrane potential and respiration and changes in expression of mitochondrial function‐related genes were observed. RNA‐sequencing analysis revealed changes in various metabolic processes, heart development, response to hypoxia, and extracellular matrix‐related activities. Metabolomic analysis revealed dysregulation of energy metabolism and increased metabolites associated with the upregulation of inflammation. Integrated omics analysis further identified functional subclusters and revealed potentially affected pathways associated with cardiac toxicities.ConclusionChronic ethanol treatment of hiPSC‐CMs resulted in overall decreased mitochondrial function, increased glycolysis, disrupted fatty acid oxidation, and impaired cardiac structural development.

Related Organizations

Emory University
United States
Instituts Universitaires de Technologie
France
Emory University School of Medicine
United States

Keywords

Ethanol, Induced Pluripotent Stem Cells, Cardiotoxicity, Mitochondria, Pregnancy, Prenatal Exposure Delayed Effects, Humans, Female, Myocytes, Cardiac, Transcriptome

Impact byBIP!

	citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	3
	popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.	Average
	influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	Average
	impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.	Average