Novel clinically relevant model of alcohol-induced cardiomyopathy associated with impaired cardiovascular function and cardiometabolic dysregulation

Authors

• J Paloczi
• Cs Matyas
• ZV Varga
• K Erdelyi
• P Mukhopadhyay
• P Pacher

Abstract

Chronic alcoholism ranks among the top five risk factors for disease and premature death. Binge drinking is the most common pattern of excessive alcohol use in the United States, particularly among young adults. Long-term, heavy alcohol consumption impairs vascular function and leads to development of cardiomyopathy and heart failure. However, reproducible and clinically relevant models of alcohol-induced cardiomyopathy in mice are lacking. Here we describe new mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH)-feeding and characterize detailed hemodynamic and metabolic alterations, mitochondrial dysfunction, and impaired redox signaling. Mice were fed with 5% EtOH for 10, 20, 40 days (d) combined with single/multiple EtOH-binges. Isocalorically pair-fed mice served as controls. Left ventricular (LV) function was assessed by sophisticated pressure-volume approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, mitochondrial biogenesis, oxidative stress markers and histopathology were also investigated. Chronic and binge EtOH-feeding was characterized by contractile dysfunction, impaired relaxation and vascular dysfunction. This was accompanied by enhanced myocardial oxidative/nitrative stress and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, myocardial hypertrophy, and excessive cardiac steatosis. The above described deleterious effects of alcohol consumption were dramatically more pronounced in groups exposed to chronic drinking combined with alcohol binges. Our results demonstrate that chronic plus binge EtOH-feeding in mice leads to alcohol-induced cardiomyopathy and vascular dysfunction. These results also suggest that combination of regular drinking with binges even within a short period of time may profoundly affect cardiac and vascular function and metabolism.

Scientific Focus Area: Molecular Biology and Biochemistry

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