Effects of chronic alcohol consumption on gene expression in the rat left ventricle: a transcriptomic analysis
4 affiliations
- 1Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center
- 2VA Nebraska-Western Iowa Healthcare System
- 3Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center
- 4Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center
Abstract
Objective: Chronic alcohol consumption is one of the leading causes of dilated cardiomyopathy. Alcohol-associated cardiomyopathy (ACM) is characterized by impaired cardiac function and ventricular dilation in individuals with a history of long-term alcohol consumption. Alcohol exerts adverse effects on the myocardium via mitochondrial dysfunction and chronic inflammation. However, the broader transcriptional changes associated with chronic alcohol exposure remain poorly understood.
Methods: A chronic ethanol feeding model was utilized, in which male Wistar rats were fed a Lieber-Decarli ethanol diet containing 6.7% (v/v) ethanol (ET) or an isocaloric control (CONT) diet for 6 weeks. Left ventricular tissues were collected from ET-fed and CONT-fed rats. Differential gene expression was assessed using bulk RNA sequencing, followed by Ingenuity Pathway Analysis (IPA).
Results: Transcriptomic analysis identified 194 upregulated and 199 downregulated genes in the left ventricles of ET-fed rats compared with CONT-fed rats. IPA revealed downregulated pathways related to the circadian clock and interferon signaling in the myocardium of ET-fed rats. In particular, the differentially altered genes included regulators of the circadian clock ( Bmal1, Npas2, Per1 , Per2 ) and interferon signaling ( Ifit2 , Ifit3 , Irf6 , Irf9 ). In contrast, pathways associated with mitochondrial RNA degradation, sheddase signaling, and neutrophil extracellular traps were upregulated in the myocardium following chronic ethanol exposure.
Conclusion: Chronic ethanol exposure is associated with dysregulation of circadian rhythm and immune-related signaling pathways in the rat myocardium. These findings highlight molecular pathways that may contribute to the development of ACM and warrant further mechanistic investigation.
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BibTeX
@article{ai2026effects,
title = {{Effects of chronic alcohol consumption on gene expression in the rat left ventricle: a transcriptomic analysis}},
author = {Weilun Ai and Carol A. Casey and Karuna Rasineni and Viswanathan Saraswathi},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1977478},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1977478/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effects of chronic alcohol consumption on gene expression in the rat left ventricle: a transcriptomic analysis
AU - Weilun Ai
AU - Carol A. Casey
AU - Karuna Rasineni
AU - Viswanathan Saraswathi
PY - 2026
DA - 2026/10/14
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1977478
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1977478/full
AB - Objective: Chronic alcohol consumption is one of the leading causes of dilated cardiomyopathy. Alcohol-associated cardiomyopathy (ACM) is characterized by impaired cardiac function and ventricular dilation in individuals with a history of long-term alcohol consumption. Alcohol exerts adverse effects on the myocardium via mitochondrial dysfunction and chronic inflammation. However, the broader transcriptional changes associated with chronic alcohol exposure remain poorly understood. Methods: A chronic ethanol feeding model was utilized, in which male Wistar rats were fed a Lieber-Decarli ethanol diet containing 6.7% (v/v) ethanol (ET) or an isocaloric control (CONT) diet for 6 weeks. Left ventricular tissues were collected from ET-fed and CONT-fed rats. Differential gene expression was assessed using bulk RNA sequencing, followed by Ingenuity Pathway Analysis (IPA). Results: Transcriptomic analysis identified 194 upregulated and 199 downregulated genes in the left ventricles of ET-fed rats compared with CONT-fed rats. IPA revealed downregulated pathways related to the circadian clock and interferon signaling in the myocardium of ET-fed rats. In particular, the differentially altered genes included regulators of the circadian clock ( Bmal1, Npas2, Per1 , Per2 ) and interferon signaling ( Ifit2 , Ifit3 , Irf6 , Irf9 ). In contrast, pathways associated with mitochondrial RNA degradation, sheddase signaling, and neutrophil extracellular traps were upregulated in the myocardium following chronic ethanol exposure. Conclusion: Chronic ethanol exposure is associated with dysregulation of circadian rhythm and immune-related signaling pathways in the rat myocardium. These findings highlight molecular pathways that may contribute to the development of ACM and warrant further mechanistic investigation.
SN - 2297-055X
ER -