Effect of Chronic Ethanol Ingestion and Gender on Heart Left Ventricular p53 Gene Expression

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2005-08, Vol.29 (8), p.1368-1373
• Main Authors: Jänkälä, Heidi, Eriksson, Peter C. J., Eklund, Kari, Sarviharju, Maija, Härkönen, Matti, Mäki, Tiina
• Format: Article
• Language: English
• Subjects: Alcoholism - genetics; Alcoholism and acute alcohol poisoning; Animals; Apoptosis - genetics; Biological and medical sciences; Cardiomyopathy, Alcoholic - genetics; DNA Damage - drug effects; DNA Damage - genetics; Ethanol - toxicity; Female; Gene Expression Regulation - drug effects; Genes, p53 - drug effects; Genes, p53 - genetics; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - pathology; Male; Medical sciences; Rats; Rats, Inbred Strains; RNA, Messenger - genetics; Sex Factors; Toxicology; Ventricular Remodeling - drug effects; Ventricular Remodeling - genetics
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1097/01.alc.0000175043.67463.e5

Background: Although the beneficial effects of mild to moderate ethanol consumption have been implied with respect to heart, alcohol abuse has proven to be a major cause of nonischemic cardiomyopathy in Western society. However, the biochemical and molecular mechanisms, which mediate the pathologic cardiac effects of ethanol, remain largely unknown. The aim of the present study was to explore the effects of chronic ethanol exposure on cardiac apoptosis and expression of some of the genes associated with cardiac remodeling in vivo. Methods: Alcohol‐avoiding Alko Non Alcohol rats of both sexes were used. The ethanol‐exposed rats (females, n= 6; males, n= 8) were given 12% (v/v) ethanol as the only available fluid from age of three to 24 months of age. The control rats (females, n= 7; males, n= 5) had only water available. At the end of the experiment, free walls of left ventricles of hearts were immediately frozen. Cytosolic DNA fragmentation, reflecting apoptosis, was measured using a commercial quantitative sandwich enzyme‐linked immunosorbent assay kit, and mRNA levels were analyzed using a quantitative reverse transcriptase–polymerase chain reaction method. Results: Ethanol treatment for two years increased cardiac left ventricular p53 mRNA levels significantly (p= 0.014) compared with control rats. The gene expression was also dependent on the gender (p= 0.001), so that male rats had higher left ventricular p53 mRNA levels than female rats. However, no significant differences in levels of DNA fragmentation were detected. Conclusions: Chronic ethanol exposure in vivo induces rat cardiac left ventricular p53 gene expression. Expression of p53 is also gender‐dependent, males having higher p53 mRNA levels than females. This preliminary finding suggests a role for the p53 gene in ethanol‐induced cardiac remodeling. The results might also have some relevance for the known gender‐dependent differences in propensity to cardiovascular disease.