e0154 Expression of tumour necrosis factor-α converting enzyme and tumour necrosis factor-α in rats with alcoholic cardiomyopathy

Purpose Chronic excessive consumption of alcohol causes ventricular remodelling and eventually leads to alcoholic cardiomyopahty (ACM). Tumour necrosis factor-α converting enzyme (TACE) has been identified to cleave membrane-bound tumour necrosis factor-α (TNF-α) to soluble TNF-α, which has crucial roles in ventricular remodelling. This study aimed to investigate the expression of TACE and TNF-α, and their impacts on ventricular remodelling in rats with ACM. Methods 50 healthy male Wistar rats were randomly divided into a control group (n=20) and an ACM group (n=30). Animals in the ACM group were given 10% alcohol ad libitum as the drinking water and 60% alcohol (5 ml/kg once per day) by intragastric administration in the first week; 10% alcohol ad libitum as the drinking water and 60% alcohol (10 ml/kg twice per day) by intragastric administration in the second week; 20% alcohol ad libitum as the drinking water and 60% alcohol (15 ml/kg twice per day) by intragastric administration from week 3 to week 16; and 30% alcohol ad libitum as the drinking water and 60% alcohol (15 ml/kg twice per day) by intragastric administration from week 17 to month 6. Animals in the control group received purified drinking water in the same regimen with alcohol treatment. Before and 6 months after initiating the study, left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), and fractional shortening (FS) were assessed by echocardiography. Six months after the study started, histopathology and ultrastructure of myocardium were examined with light and electron microscopy; mRNA expression of TACE was evaluated by real-time PCR; and protein expression of TACE and TNF-α was analysed using immunohistochemistry and western blot, respectively. Results Following 6 months of alcohol feeding, LVEF and FS were reduced (p<0.05 for all), while LVEDD was augmented in the ACM group (p<0.05), as compared with the control group. Severe changes in cardiac structure were also seen in the ACM group. The mRNA and protein expression of TACE and the protein expression of TNF-α were up-regulated in the ACM group in comparison with the control group (p<0.05 for all). In both groups, the protein expression of TACE positively correlated with that of TNF-α (p<0.01) and LVEDD, whereas it negatively correlated with LVEF (p<0.05). Conclusions TACE is over-expressed in the ventricle of ACM rats, and may involve in the process of ventricular remodelling via cleaving TNF-α. Therefore, TACE may represent a new therapeutic target in the prevention and treatment of ventricular remodelling in ACM.