[Roles of PYK2 and caveolin-1 in alcoholic cardiomyopathy and the effect of drug intervention].

ABSTRACT

OBJECTIVE: To explore the protein expressions of PYK2 (protein-rich tyrosine kinase-2) and caveolin-1 in alcoholic cardiomyopathy (ACM) dog model and the effect of early drug intervention. METHODS: A total of 28 adult dogs were randomly divided into 4 groups (i) alcohol-fed; (ii) alcohol plus valsartan, an angiotensin receptor blocker (ARB); (iii) alcohol plus carnitine; (iv) control group. At Month 6, the cardiac functions of all animals were evaluated by echocardiography. The concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in cardiac tissue were detected by chronometry. The protein expressions of collagen types I and III were determined by ELISA (enzyme-linked immunosorbent assay) while those of PYK2 and caveolin-1 evaluated by immunohistochemistry. The internal relationship of PYK2, caveolin-1, MDA and collagen types I & III was analyzed. RESULTS: Compared with the control group, the contents of SOD and GSH-Px significantly decreased in the alcohol, valsartan and carnitine groups while MDA significantly increased in the alcohol and carnitine groups. The relative contents in each group were as follows MDA [alcohol (28 ± 5) U/mg Pro; valsartan (33 ± 13) U/mg Pro; carnitine (33 ± 10) U/mg Pro], GSH-Px [alcohol (188 ± 37) U/g Pro; valsartan (362 ± 29) U/g Pro; carnitine (282 ± 29) U/g Pro and MDA [alcohol (19.4 ± 3.0) nmol/mg Pro; carnitine (10.8 ± 2.1) nmol/mg Pro]. Compared with the control group, the concentration of collagen typeI significantly increased in the alcohol, valsartan and carnitine groups. In the alcohol-fed group, the protein expression of PYK2 gradually increased with the progression of ACM while that of caveolin-1 stayed at a low level. Through the interventions of valsartan and carnitine, the protein expression of PYK2 significantly increased while that of caveolin-1 significantly decreased (all P < 0.01). CONCLUSION: Alcohol promotes the myocardial oxidative stress and fibrosis through an elevated expression of PYK2 and a lowered expression of caveolin-1. Then a deterioration of cardiac structures and functions occur.