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Alterations in Cardiac Structure and Function in a Murine Model of Chronic Alcohol Consumption

Published online by Cambridge University Press:  09 May 2012

Brittany A. Law*
Affiliation:
Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
Scott P. Levick
Affiliation:
Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
Wayne E. Carver
Affiliation:
Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
*
Corresponding author. E-mail: Brittany.Law@uscmed.sc.edu
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Abstract

Male, wild-type, FVB strain mice were fed a nutritionally complete liquid diet supplemented with 4% ethanol v/v over a time course of 1, 2, 4, 8, 12, and 14 weeks. Controls were offered an isocaloric liquid equivalent and pair fed with their ethanol counterparts. Changes in cardiac physiology were assessed at respective time points via echocardiography. Additionally, the use of histological techniques, mRNA analysis, apoptosis determination, and immunohistochemistry were employed to determine the functional and structural changes on the heart. Echocardiograph analysis revealed a compensatory phase that occurred early in the time course (1–8 weeks) and decompensation reverting toward heart failure at weeks 12 and 14. Throughout the study, an increase in cardiomyocyte hypertrophy, cardiac fibrosis, apoptosis, TGF-β, and the presence of α-SMA-positive cells were determined. A compensatory period in mice treated with ethanol occurred early followed by a transition to a dilated phenotype over time. A number of factors may be involved in this process including the activation of myofibroblasts and their fibrotic activities that is correlated with the presence of transforming growth factor beta.

Type
Biological Applications
Copyright
Copyright © Microscopy Society of America 2012

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References

Askanas, A., Udoshi, M. & Sadjadi, S.A. (1980). The heart in chronic alcoholism: A noninvasive study. Am Heart J 99, 916.CrossRefGoogle ScholarPubMed
Baraona, E., Leo, M.A., Borowsky, S.A. & Lieber, C.S. (1975). Alcoholic hepatomegaly: Accumulation of protein in the liver. Science 190, 794795.CrossRefGoogle ScholarPubMed
Bedossa, P., Peltier, E., Terris, B., Franco, D. & Poynard, T. (1995). Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 1 receptors in normal, cirrhotic, and neoplastic human livers. Hepatology 21, 760766.Google ScholarPubMed
Boé, D.M., Vandivier, R.W., Burnham, E.L. & Moss, M. (2009). Alcohol abuse and pulmonary disease. J Leukoc Biol 86, 10971104.CrossRefGoogle ScholarPubMed
Carabello, B.A. (2002). Concentric versus eccentric remodeling. J Card Fail 8, S258S263.CrossRefGoogle ScholarPubMed
Dancy, M. & Maxwell, J.D. (1986). Alcohol and dilated cardiomyopathy. Alcohol Alcohol 21, 185198.Google ScholarPubMed
Djoussé, L. & Gaziano, J.M. (2008). Alcohol consumption and heart failure: A systematic review. Curr Atheroscler Rep 10, 117120.CrossRefGoogle ScholarPubMed
Dobaczewski, M., Chen, W. & Frangogiannis, N.G. (2011). Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol 51, 600606.CrossRefGoogle ScholarPubMed
Doser, T.A., Turdi, S., Thomas, D.P., Epstein, P.N., Li, S.Y. & Ren, J. (2009). Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation 119, 19411949.CrossRefGoogle ScholarPubMed
Fernández-Solà, J., Fatjó, F., Sacanella, E., Estruch, R., Bosch, X., Urbano-Márquez, A. & Nicolás, J.M. (2006). Evidence of apoptosis in alcoholic cardiomyopathy. Hum Pathol 37, 11001110.CrossRefGoogle ScholarPubMed
Gerdes, A.M. (2002). Cardiac myocyte remodeling in hypertrophy and progression to failure. J Card Fail 8, S264S268.CrossRefGoogle ScholarPubMed
Heger, J., Warga, B., Meyering, B., Abdallah, Y., Schlüter, K.D., Piper, H.M. & Euler, G. (2011). TGFβ receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release. J Cell Physiol 226, 26832690.CrossRefGoogle ScholarPubMed
Kim, S.D., Bieniarz, T., Esser, K.A. & Piano, M.R. (2003). Cardiac structure and function after short-term ethanol consumption in rats. Alcohol 29, 2129.CrossRefGoogle ScholarPubMed
Kliment, C.R., Suliman, H.B., Tobolewski, J.M., Reynolds, C.M., Day, B.J., Zhu, X., McTiernan, C.F., McGaffin, K.R., Piantadosi, C.A. & Oury, T.D. (2009). Extracellular superoxide dismutase regulates cardiac function and fibrosis. J Mol Cell Cardiol 47, 730742.CrossRefGoogle ScholarPubMed
Laonigro, I., Correale, M., Di Biase, M. & Altomare, E. (2009). Alcohol abuse and heart failure. Eur J Heart Fail 11, 453462.CrossRefGoogle ScholarPubMed
Li, S.Y., Gilbert, S.A., Li, Q. & Ren, J. (2009). Aldehyde dehydrogenase-2 (ALDH2) ameliorates chronic alcohol ingestion-induced myocardial insulin resistance and endoplasmic reticulum stress. J Mol Cell Cardiol 47, 247255.CrossRefGoogle ScholarPubMed
Lieber, C.S. & DeCarli, L.M. (1982). The feeding of alcohol in liquid diets: Two decades of applications and 1982 update. Alcohol Clin Exp Res 6, 523531.CrossRefGoogle ScholarPubMed
Melchior-Becker, A., Dai, G., Ding, Z., Schäfer, L., Schrader, J., Young, M.F. & Fischer, J.W. (2011). Deficiency of biglycan causes cardiac fibroblasts to differentiate into a myofibroblast phenotype. J Biol Chem 286, 1736517375.CrossRefGoogle ScholarPubMed
Pauschinger, M., Knopf, D., Petschauer, S., Doerner, A., Poller, W., Schwimmbeck, P.L., Kühl, U. & Schultheiss, H.P. (1999). Dilated cardiomyopathy is associated with significant changes in collagen type I/III ratio. Circulation 99, 27502756.CrossRefGoogle ScholarPubMed
Rameckers, J., Hummel, S. & Herrmann, B. (1997). How many cycles does a PCR need? Determinations of cycle numbers depending on the number of targets and the reaction efficiency factor. Naturwissenschaften 84, 259262.CrossRefGoogle ScholarPubMed
Savolainen, V.T., Liesto, K., Männikkö, A., Penttilä, A. & Karhunen, P.J. (1993). Alcohol consumption and alcoholic liver disease: Evidence of a threshold level of effects of ethanol. Alcohol Clin Exp Res 17, 11121117.CrossRefGoogle ScholarPubMed
Schiller, N.B., Shah, P.M., Crawford, M., DeMaria, A., Devereux, R., Feigenbaum, H., Gutgesell, H., Reichek, N., Sahn, D., Schnittger, I., Silverman, N.H. & Tajik, A.J. (1989). Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2, 358367.CrossRefGoogle ScholarPubMed
Seth, D., D'Souza El-Guindy, N.B., Apte, M., Mari, M., Dooley, S., Neuman, M., Haber, P.S., Kundu, G.C., Darwanto, A., de Villiers, W.J., Vonlaufen, A., Xu, Z., Phillips, P., Yang, S., Goldstein, D., Pirola, R.M., Wilson, J.S., Moles, A., Fernández, A., Colell, A., García-Ruiz, C., Fernández-Checa, J.C., Meyer, C. & Meindl-Beinker, N.M. (2009). Alcohol, signaling, and ECM turnover. Alcohol Clin Exp Res 34, 115.Google ScholarPubMed
Silberbauer, K., Juhasz, M., Ohrenberger, G. & Hess, C. (1988). Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in young alcoholics. Cardiology 75, 431439.CrossRefGoogle ScholarPubMed
Spanagel, R. (2009). Alcoholism: A systems approach from molecular physiology to addictive behavior. Physiol Rev 89, 649705.CrossRefGoogle ScholarPubMed
Takimoto, E., Champion, H.C., Li, M., Belardi, D., Ren, S., Rodriguez, E.R., Bedja, D., Gabrielson, K.L., Wang, Y. & Kass, D.A. (2005). Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11, 214222.CrossRefGoogle ScholarPubMed
Yang, K.L., Chang, W.T., Hung, K.C., Li, E.I. & Chuang, C.C. (2008). Inhibition of transforming growth factor-beta-induced liver fibrosis by a retinoic acid derivative via the suppression of Col 1A2 promoter activity. Biochem Biophys Res Commun 373, 219223.CrossRefGoogle ScholarPubMed
Yu, J., Wu, C.W., Chu, E.S., Hui, A.Y., Cheng, A.S., Go, M.Y., Ching, A.K., Chui, Y.L., Chan, H.L. & Sung, J.J. (2008). Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice. Biochem Biophys Res Commun 372, 571577.CrossRefGoogle ScholarPubMed
Zhang, B., Turdi, S., Li, Q., Lopez, F.L., Eason, A.R., Anversa, P. & Ren, J. (2010). Cardiac overexpression of insulin-like growth factor 1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction but not hypertrophy: Roles of Akt, mTOR, GSK3beta, and PTEN. Free Radic Biol Med 49, 12381253.CrossRefGoogle Scholar
Zhang, J.H. & Xu, M. (2000). DNA fragmentation in apoptosis. Cell Res 10, 205211.CrossRefGoogle ScholarPubMed