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A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption-Alcoholic Cardiomyopathy.

ABSTRACT: Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson's trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.

SUBMITTER: Cao Z

PROVIDER: S-EPMC8070378 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe global impact of alcohol consumption on deaths due to cardiomyopathy (CM) has not been quantified to date, even though CM contains a subcategory for alcoholic CM with an effect of heavy drinking over time as the postulated underlying causal mechanism. In this feasibility study, a model to estimate the alcohol-attributable fraction (AAF) of CM deaths based on alcohol exposure measures is proposed.MethodsA two-step model was developed based on aggregate-level data from 95 countries, including the most populous (data from 2013 or last available year). First, the crude mortality rate of alcoholic CM per 1,000,000 adults was predicted using a negative binomial regression based on prevalence of alcohol use disorders (AUD) and adult alcohol per capita consumption (APC) (n?=?52 countries). Second, the proportion of alcoholic CM among all CM deaths (i.e., AAF) was predicted using a fractional response probit regression with alcoholic CM crude mortality rate (from Step 1), AUD prevalence, APC per drinker, and Global Burden of Disease region as predictions. Additional models repeated these steps by sex and for the wider Global Burden of Disease study definition of CM.ResultsThere were strong correlations (>0.9) between the crude mortality rate of alcoholic CM and the AAFs, supporting the modeling strategy. In the first step, the population-weighted mean crude mortality rate was estimated at 8.4 alcoholic CM deaths per 1,000,000 (95% CI: 7.4-9.3). In the second step, the global AAFs were estimated at 6.9% (95% CI: 5.4-8.4%). Sex-specific figures suggested a lower AAF among females (2.9%, 95% CI: 2.3-3.4%) as compared to males (8.9%, 95% CI: 7.0-10.7%). Larger deviations between observed and predicted AAFs were found in Eastern Europe and Central Asia.ConclusionsThe model proposed promises to fill the gap to include AAFs for CM into comparative risk assessments in the future. These predictions likely will be underestimates because of the stigma involved in all fully alcohol-attributable conditions and subsequent problems in coding of alcoholic CM deaths.

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A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption-Alcoholic Cardiomyopathy.

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