Transcriptome Analysis Of Non-coding RNAs Of Myocardia In Mice With Alcoholic Cardiomyopathy

Objective:Chronically heavy alcohol consumption may result in a number of cellular, histological and structural changes in important organs, leading to gastric ulcer, pancreatitis, alcoholic fatty liver and alcoholic cardiomyopathy. In this paper, alcoholic cardiomyopathy is the main study objective, we screened the differentially expressed microRNAs, long non-coding RNAs and circular RNAs in myocardia in mice fed with alcohol for 24 weeks by high-throughput microarray. It will help us reveal molecular mechanism underlying alcoholic cardiomyopathy.Method:One hundred Kunming mice (12-14 week-old) were randomly divided into alcohol group (n=60) and control group (n=40). Four percent alcohol was the only source of drinking water for alcohol group. The mice have drunk alcohol ad libitum for 24 weeks to construct alcoholic cardiomyopathy. After 24-week feeding, five hearts were harvested from each group mice to prepare paraffin sections and ultrathin sections and to examine histological changes and ultrastructural changes under optical microscope and transmission electron microscopy. After we had confirmed development of alcoholic cardiomyopathy in alcohol group, we screened differentially expressed microRNAs, long non-coding RNAs, circular RNAs and mRNAs in three heart samples of each group by high-throughput microarray. We analyzed gene functions and signal pathways of differentially expressed mRNAs by bioinformatic software to find some mRNAs and their biological signal pathways closely related with alcoholic cardiomyopathy.Results:1. Optic microscope examination indicated that thickness of interventricular septum in alcohol-exposed hearts was significantly increased compared to that in control hearts. Transmission electron microscopic images exhibited fragments and disarray of myofibrils in cardiomyocytes, vacuolization of cardiomyocytes, dilated sarcoplasmic reticulum, and more swollen mitochondria with disorganized and degenerated cristae.2. Compared to control group,19 microRNAs,494 long non-coding RNAs,265 circular RNAs and 404 mRNAs differentially expressed in alcohol treated group (p<0.05).3. After analyzing gene functions and signal pathways by bioinformatic software, we found that differentially expressed mRNAs were associated with carbohydrate metabolism.Conclusion:1. Chronically heavy alcohol consumption leads to cardiac remodeling and disruption of myofibril, mitochondria, and sarcoplasmic reticulum.2. Chronic alcohol consumption can change non-coding RNAs profile and mRNA profile of heart tissue.