Research Article: Effects of chronic alcohol consumption on gene expression in the rat left ventricle: a transcriptomic analysis
Abstract:
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.
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).
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.
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.
Introduction:
Chronic heavy alcohol consumption is an important cause of dilated cardiomyopathy and can lead to alcohol-associated cardiomyopathy (ACM), which accounts for approximately 10% of dilated cardiomyopathy ( 1 ). ACM is characterized by ventricular dilation and impaired cardiac function ( 2 ). Chronic alcohol exposure promotes myocardial hypertrophy and dysfunction through multiple mechanisms, including inflammation, nitrative/oxidative stress, and increased collagen deposition in rats ( 3 , 4 ). However, the…
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