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Chronic Ethanol Exposure Induces Deleterious Changes in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

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Abstract

Chronic alcohol consumption in adults can induce cardiomyopathy, arrhythmias, and heart failure. In newborns, prenatal alcohol exposure can increase the risk of congenital heart diseases. Understanding biological mechanisms involved in the long-term alcohol exposure-induced cardiotoxicity is pivotal to the discovery of therapeutic strategies. In this study, cardiomyocytes derived from human pluripotent stem cells (hiPSC-CMs) were treated with clinically relevant doses of ethanol for various durations up to 5 weeks. The treated cells were characterized for their cellular properties and functions, and global proteomic profiling was conducted to understand the molecular changes associated with long-term ethanol exposure. Increased cell death, oxidative stress, deranged Ca2+ handling, abnormal action potential, altered contractility, and suppressed structure development were observed in ethanol-treated cells. Many dysregulated proteins identified by global proteomic profiling were involved in apoptosis, heart contraction, and extracellular collagen matrix. In addition, several signaling pathways including the Wnt and TGFβ signaling pathways were affected due to long-term ethanol treatment. Therefore, chronic ethanol treatment of hiPSC-CMs induces cardiotoxicity, impairs cardiac functions, and alters protein expression and signaling pathways. This study demonstrates the utility of hiPSC-CMs as a novel model for chronic alcohol exposure study and provides the molecular mechanisms associated with long-term alcohol exposure in human cardiomyocytes.

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Data Availability

The raw files of proteomics have been deposited in the public MassIVE database with the identifier MSV000087349.

References

  1. Degenhardt, L., Chiu, W. T., Sampson, N., Kessler, R. C., Anthony, J. C., Angermeyer, M., Bruffaerts, R., de Girolamo, G., Gureje, O., Huang, Y., et al. (2008) Toward a global view of alcohol, tobacco, cannabis, and cocaine use: Findings from the WHO world mental health surveys. PLoS Med, 5(7), e141.

  2. World Health Organization. Global status report on alcohol and health. Available at: https://apps.who.int/iris/bitstream/handle/10665/274603/9789241565639-eng.pdf?ua=1 (Accessed 27 Feb 2021).

  3. Fernandez-Sola, J. (2020). The effects of ethanol on the heart: Alcoholic cardiomyopathy. Nutrients, 12(2), 572.

    Article  CAS  PubMed Central  Google Scholar 

  4. Erol, A., & Karpyak, V. M. (2015). Sex and gender-related differences in alcohol use and its consequences: Contemporary knowledge and future research considerations. Drug and Alcohol Dependence, 156, 1–13.

    Article  PubMed  Google Scholar 

  5. Mogos, M. F., Salemi, J. L., Phillips, S. A., & Piano, M. R. (2019). Contemporary appraisal of sex differences in prevalence, correlates, and outcomes of alcoholic cardiomyopathy. Alcohol and Alcoholism, 54(4), 386–395.

    Article  PubMed  Google Scholar 

  6. Urbano-Marquez, A., Estruch, R., Fernandez-Sola, J., Nicolas, J. M., Pare, J. C., & Rubin, E. (1995). The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men. JAMA, 274(2), 149–154.

    Article  CAS  PubMed  Google Scholar 

  7. Centers for Disease Control and Prevention. Excessive alcohol use is a risk to women's health. Available at: https://www.cdc.gov/alcohol/fact-sheets/womens-health.htm (Accessed 27 Feb 2021).

  8. Centers for Disease Control and Prevention. Fetal alcohol spectrum disorders. Available at: https://www.cdc.gov/ncbddd/fasd/data.html (Accessed 1 Mar 2021).

  9. Burd, L., Deal, E., Rios, R., Adickes, E., Wynne, J., & Klug, M. G. (2007). Congenital heart defects and fetal alcohol spectrum disorders. Congenital Heart Disease, 2(4), 250–255.

    Article  PubMed  Google Scholar 

  10. El-Mas, M. M., & Abdel-Rahman, A. A. (2014). Nongenomic effects of estrogen mediate the dose-related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats. American journal of physiology. Endocrinology and metabolism, 306(7), E740-747.

    Article  CAS  PubMed  Google Scholar 

  11. Zhu, Z., Huang, Y., Lv, L., Tao, Y., Shao, M., Zhao, C., Xue, M., Sun, J., Niu, C., Wang, Y., et al. (2018). Acute ethanol exposure-induced autophagy-mediated cardiac injury via activation of the ROS-JNK-Bcl-2 pathway. Journal of Cellular Physiology, 233(2), 924–935.

    Article  CAS  PubMed  Google Scholar 

  12. Mustroph, J., Wagemann, O., Lebek, S., Tarnowski, D., Ackermann, J., Drzymalski, M., Pabel, S., Schmid, C., Wagner, S., Sossalla, S., et al. (2018). SR Ca(2+)-leak and disordered excitation-contraction coupling as the basis for arrhythmogenic and negative inotropic effects of acute ethanol exposure. Journal of Molecular and Cellular Cardiology, 116, 81–90.

    Article  CAS  PubMed  Google Scholar 

  13. Rampoldi, A., Singh, M., Wu, Q., Duan, M., Jha, R., Maxwell, J. T., Bradner, J. M., Zhang, X., Saraf, A., Miller, G. W., et al. (2019). Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicological Sciences, 169(1), 280–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mouton, A. J., El Hajj, E. C., Ninh, V. K., Siggins, R. W., & Gardner, J. D. (2020). Inflammatory cardiac fibroblast phenotype underlies chronic alcohol-induced cardiac atrophy and dysfunction. Life Sciences, 245, 117330.

  15. Yang, M., Wang, S., Fu, S., Wu, N. N., Xu, X., Sun, S., Zhang, Y., & Ren, J. (2021). Deletion of the E3 ubiquitin ligase, Parkin, exacerbates chronic alcohol intake-induced cardiomyopathy through an Ambra1-dependent mechanism. British Journal of Pharmacology, 178(4), 964–982.

    Article  CAS  PubMed  Google Scholar 

  16. Nakashima, M. A., Silva, C. B. P., Gonzaga, N. A., Simplicio, J. A., Omoto, A. C. M., Tirapelli, L. F., Tanus-Santos, J. E., & Tirapelli, C. R. (2019). Chronic ethanol consumption increases reactive oxygen species generation and the synthesis of pro-inflammatory proteins in the heart through TNFR1-dependent mechanisms. Cytokine, 121, 154734.

  17. Wang, W., Liu, T., Liu, Y., Yu, L., Yan, X., Weng, W., Lu, X., & Zhang, C. (2021). Astaxanthin attenuates alcoholic cardiomyopathy via inhibition of endoplasmic reticulum stress-mediated cardiac apoptosis. Toxicol and Applied Pharmacology, 412, 115378.

  18. Ninh, V. K., El Hajj, E. C., Ronis, M. J., & Gardner, J. D. (2019). N-acetylcysteine prevents the decreases in cardiac collagen I/III ratio and systolic function in neonatal mice with prenatal alcohol exposure. Toxicology Letters, 315, 87–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nguyen, V. B., Probyn, M. E., Campbell, F., Yin, K. V., Samuel, C. S., Zimanyi, M. A., Bertram, J. F., Black, M. J., & Moritz, K. M. (2014). Low-dose maternal alcohol consumption: Effects in the hearts of offspring in early life and adulthood. Physiological Reports, 2(7), e12087.

  20. Ren, J., Wold, L. E., Natavio, M., Ren, B. H., Hannigan, J. H., & Brown, R. A. (2002). Influence of prenatal alcohol exposure on myocardial contractile function in adult rat hearts: Role of intracellular calcium and apoptosis. Alcohol and Alcoholism, 37(1), 30–37.

    Article  CAS  PubMed  Google Scholar 

  21. Sarmah, S., & Marrs, J. A. (2017). Embryonic ethanol exposure affects early- and late-added cardiac precursors and produces long-lasting heart chamber defects in zebrafish. Toxics, 5(4), 35.

    Article  PubMed Central  Google Scholar 

  22. Guo, G. R., Chen, L., Rao, M., Chen, K., Song, J. P., & Hu, S. S. (2018). A modified method for isolation of human cardiomyocytes to model cardiac diseases. Journal of Translational Medicine, 16(1), 288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mitcheson, J. S., Hancox, J. C., & Levi, A. J. (1998). Cultured adult cardiac myocytes: Future applications, culture methods, morphological and electrophysiological properties. Cardiovascular Research, 39(2), 280–300.

    Article  CAS  PubMed  Google Scholar 

  24. Hnatiuk, A. P., Briganti, F., Staudt, D. W., & Mercola, M. (2021). Human iPSC modeling of heart disease for drug development. Cell Chemical Biology, 28(3), 271–282.

    Article  CAS  PubMed  Google Scholar 

  25. Knight, W. E., Cao, Y., Lin, Y. H., Chi, C., Bai, B., Sparagna, G. C., Zhao, Y., Du, Y., Londono, P., Reisz, J. A., et al. (2021). Maturation of pluripotent stem cell-derived cardiomyocytes enables modeling of human hypertrophic cardiomyopathy. Stem Cell Reports, 16(3), 519–533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kamdar, F., Das, S., Gong, W., Klaassen Kamdar, A., Meyers, T. A., Shah, P., Ervasti, J. M., Townsend, D., Kamp, T. J., Wu, J. C., et al. (2020). Stem cell-derived cardiomyocytes and beta-adrenergic receptor blockade in Duchenne muscular dystrophy cardiomyopathy. Journal of the American College of Cardiology, 75(10), 1159–1174.

    Article  CAS  PubMed  Google Scholar 

  27. McDermott-Roe, C., Lv, W., Maximova, T., Wada, S., Bukowy, J., Marquez, M., Lai, S., Shehu, A., Benjamin, I., Geurts, A., et al. (2019). Investigation of a dilated cardiomyopathy-associated variant in BAG3 using genome-edited iPSC-derived cardiomyocytes. JCI Insight, 4(22), e128799.

  28. Kitani, T., Ong, S. G., Lam, C. K., Rhee, J. W., Zhang, J. Z., Oikonomopoulos, A., Ma, N., Tian, L., Lee, J., Telli, M. L., et al. (2019). Human induced pluripotent stem cell model of trastuzumab-induced cardiac dysfunction in breast cancer patients. Circulation, 139(21), 2451–2465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu, R., Li, D., Sun, F., Rampoldi, A., Maxwell, J. T., Wu, R., Fischbach, P., Castellino, S. M., Du, Y., Fu, H., et al. (2020). Melphalan induces cardiotoxicity through oxidative stress in cardiomyocytes derived from human induced pluripotent stem cells. Stem Cell Research & Therapy, 11(1), 470.

    Article  CAS  Google Scholar 

  30. Liu, R., Sun, F., Forghani, P., Armand, L. C., Rampoldi, A., Li, D., Wu, R., & Xu, C. (2020). Proteomic profiling reveals roles of stress response, Ca(2+) transient dysregulation, and novel signaling pathways in alcohol-induced cardiotoxicity. Alcoholism, Clinical and Experimental Research, 44(11), 2187–2199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rhee, J. W., Yi, H., Thomas, D., Lam, C. K., Belbachir, N., Tian, L., Qin, X., Malisa, J., Lau, E., Paik, D. T., et al. (2020). Modeling secondary iron overload cardiomyopathy with human induced pluripotent stem cell-derived cardiomyocytes. Cell Reports, 32(2), 107886.

  32. Jha, R., Xu, R. H., & Xu, C. (2015). Efficient differentiation of cardiomyocytes from human pluripotent stem cells with growth factors. Methods in Molecular Biology, 1299, 115–131.

    Article  CAS  PubMed  Google Scholar 

  33. Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., et al. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology, 25(9), 1015–1024.

    Article  CAS  PubMed  Google Scholar 

  34. Jha, R., Wu, Q., Singh, M., Preininger, M. K., Han, P., Ding, G., Cho, H. C., Jo, H., Maher, K. O., Wagner, M. B., et al. (2016). Simulated microgravity and 3D culture enhance induction, viability, proliferation and differentiation of cardiac progenitors from human pluripotent stem cells. Science and Reports, 6, 30956.

    Article  CAS  Google Scholar 

  35. Brahm, J. (1983) Permeability of human red cells to a homologous series of aliphatic alcohols. Limitations of the continuous flow-tube method. Journal of General Physiology, 81(2), 283–304.

  36. Gentillon, C., Li, D., Duan, M., Yu, W. M., Preininger, M. K., Jha, R., Rampoldi, A., Saraf, A., Gibson, G. C., Qu, C. K., et al. (2019). Targeting HIF-1alpha in combination with PPARalpha activation and postnatal factors promotes the metabolic maturation of human induced pluripotent stem cell-derived cardiomyocytes. Journal of Molecular and Cellular Cardiology, 132, 120–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Huebsch, N., Loskill, P., Mandegar, M. A., Marks, N. C., Sheehan, A. S., Ma, Z., Mathur, A., Nguyen, T. N., Yoo, J. C., Judge, L. M., et al. (2015). Automated video-based analysis of contractility and calcium flux in human-induced pluripotent stem cell-derived cardiomyocytes cultured over different spatial scales. Tissue Engineering. Part C, Methods, 21(5), 467–479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A. H., Tanaseichuk, O., Benner, C., & Chanda, S. K. (2019). Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nature Communications, 10(1), 1523.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Intoximeters. Alcohol and the human body. Available at: https://www.intox.com/physiology/ (Accessed 27 Feb 2021).

  40. Han, J., Wu, Q., **a, Y., Wagner, M. B., & Xu, C. (2016). Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation. Stem Cell Res, 16(3), 740–750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Correia, C., Koshkin, A., Duarte, P., Hu, D., Carido, M., Sebastiao, M. J., Gomes-Alves, P., Elliott, D. A., Domian, I. J., Teixeira, A. P., et al. (2018). 3D aggregate culture improves metabolic maturation of human pluripotent stem cell derived cardiomyocytes. Biotechnology and Bioengineering, 115(3), 630–644.

    Article  CAS  PubMed  Google Scholar 

  42. Fiedler, L. R., Chapman, K., **e, M., Maifoshie, E., Jenkins, M., Golforoush, P. A., Bellahcene, M., Noseda, M., Faust, D., Jarvis, A., et al. (2019). MAP4K4 inhibition promotes survival of human stem cell-derived cardiomyocytes and reduces infarct size in vivo. Cell Stem Cell, 24(4), 579–591 e512.

  43. Langhans, S. A. (2018). Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Frontiers in Pharmacology, 9, 6.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Duval, K., Grover, H., Han, L. H., Mou, Y., Pegoraro, A. F., Fredberg, J., & Chen, Z. (2017). Modeling physiological events in 2D vs. 3D cell culture. Physiology (Bethesda), 32(4), 266–277.

  45. Park, S. J., Zhang, D., Qi, Y., Li, Y., Lee, K. Y., Bezzerides, V. J., Yang, P., **a, S., Kim, S. L., Liu, X., et al. (2019). Insights into the pathogenesis of catecholaminergic polymorphic ventricular tachycardia from engineered human heart tissue. Circulation, 140(5), 390–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ellermann, C., Mittelstedt, A., Wolfes, J., Willy, K., Leitz, P., Reinke, F., Eckardt, L., & Frommeyer, G. (2020). Action potential triangulation explains acute proarrhythmic effect of aliskiren in a whole-heart model of atrial fibrillation. Cardiovascular Toxicology, 20(1), 49–57.

    Article  CAS  PubMed  Google Scholar 

  47. Lan, H., Xu, Q., El-Battrawy, I., Zhong, R., Li, X., Lang, S., Cyganek, L., Borggrefe, M., Zhou, X., & Akin, I. (2020). Ionic mechanisms of disopyramide prolonging action potential duration in human-induced pluripotent stem cell-derived cardiomyocytes from a patient with short QT syndrome type 1. Frontiers in Pharmacology, 11, 554422.

  48. Song, Z., Ko, C. Y., Nivala, M., Weiss, J. N., & Qu, Z. (2015). Calcium-voltage coupling in the genesis of early and delayed afterdepolarizations in cardiac myocytes. Biophysical Journal, 108(8), 1908–1921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Landstrom, A. P., Dobrev, D., & Wehrens, X. H. T. (2017). Calcium signaling and cardiac arrhythmias. Circulation Research, 120(12), 1969–1993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sutanto, H., Cluitmans, M. J. M., Dobrev, D., Volders, P. G. A., Bebarova, M., & Heijman, J. (2020). Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses. Journal of Molecular and Cellular Cardiology, 146, 69–83.

    Article  CAS  PubMed  Google Scholar 

  51. Tse, G., Yan, B. P., Chan, Y. W., Tian, X. Y., & Huang, Y. (2016). Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: The link with cardiac arrhythmogenesis. Frontiers in Physiology, 7, 313.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Gautel, M., & D**ovic-Carugo, K. (2016). The sarcomeric cytoskeleton: From molecules to motion. Journal of Experimental Biology, 219(Pt 2), 135–145.

    Article  Google Scholar 

  53. Fernandez-Sola, J., Nicolas, J. M., Pare, J. C., Sacanella, E., Fatjo, F., Cofan, M., & Estruch, R. (2000). Diastolic function impairment in alcoholics. Alcoholism, Clinical and Experimental Research, 24(12), 1830–1835.

    Article  CAS  PubMed  Google Scholar 

  54. Guan, Z., Lui, C. Y., Morkin, E., & Bahl, J. J. (2004). Oxidative stress and apoptosis in cardiomyocyte induced by high-dose alcohol. Journal of Cardiovascular Pharmacology, 44(6), 696–702.

    Article  CAS  PubMed  Google Scholar 

  55. Schieber, M., & Chandel, N. S. (2014). ROS function in redox signaling and oxidative stress. Current Biology, 24(10), R453-462.

    Article  CAS  PubMed  Google Scholar 

  56. Xu, T., Ding, W., Ji, X., Ao, X., Liu, Y., Yu, W., & Wang, J. (2019). Oxidative stress in cell death and cardiovascular diseases. Oxidative Medicine and Cellular Longevity, 2019, 9030563.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Rienks, M., Papageorgiou, A. P., Frangogiannis, N. G., & Heymans, S. (2014). Myocardial extracellular matrix: An ever-changing and diverse entity. Circulation Research, 114(5), 872–888.

    Article  CAS  PubMed  Google Scholar 

  58. Bildyug, N. (2019). Extracellular matrix in regulation of contractile system in cardiomyocytes. International Journal of Molecular Sciences, 20(20), 5054.

    Article  CAS  PubMed Central  Google Scholar 

  59. Bi, X., Song, Y., Song, Y., Yuan, J., Cui, J., Zhao, S., & Qiao, S. (2021). Collagen cross-linking is associated with cardiac remodeling in hypertrophic obstructive cardiomyopathy. Journal of the American Heart Association, 10(1), e017752.

  60. Johnson, R., Nxele, X., Cour, M., Sangweni, N., Jooste, T., Hadebe, N., Samodien, E., Benjeddou, M., Mazino, M., Louw, J., et al. (2020). Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model. Science and Reports, 10(1), 12352.

    Article  CAS  Google Scholar 

  61. Hua, X., Wang, Y. Y., Jia, P., **ong, Q., Hu, Y., Chang, Y., Lai, S., Xu, Y., Zhao, Z., & Song, J. (2020). Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression. BMC Medicine, 18(1), 2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Liu, G., Ma, C., Yang, H., & Zhang, P. Y. (2017). Transforming growth factor beta and its role in heart disease. Experimental and Therapeutic Medicine, 13(5), 2123–2128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dawson, K., Aflaki, M., & Nattel, S. (2013). Role of the Wnt-Frizzled system in cardiac pathophysiology: A rapidly develo**, poorly understood area with enormous potential. Journal of Physiology, 591(6), 1409–1432.

    Article  Google Scholar 

  64. Yousefi, F., Shabaninejad, Z., Vakili, S., Derakhshan, M., Movahedpour, A., Dabiri, H., Ghasemi, Y., Mahjoubin-Tehran, M., Nikoozadeh, A., Savardashtaki, A., et al. (2020). TGF-beta and WNT signaling pathways in cardiac fibrosis: Non-coding RNAs come into focus. Cell Communication and Signaling: CCS, 18(1), 87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Landry, N. M., Cohen, S., & Dixon, I. M. C. (2018). Periostin in cardiovascular disease and development: A tale of two distinct roles. Basic Research in Cardiology, 113(1), 1.

    Article  CAS  PubMed  Google Scholar 

  66. Gross, J. C., & Zelarayan, L. C. (2018). The mingle-mangle of Wnt signaling and extracellular vesicles: Functional implications for heart research. Frontiers in Cardiovascular Medicine, 5, 10.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Hanna, A., & Frangogiannis, N. G. (2019). The role of the TGF-beta superfamily in myocardial infarction. Frontiers in Cardiovascular Medicine, 6, 140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Changfa Shu, Dr. Yuhong Du and Dr. Haian Fu at Emory Chemical Biology Discovery Center and the Department of Pharmacology and Chemical Biology, Emory University School of Medicine for their support on the ImageXpress Micro XLS System and Guava easyCyte Flow Cytometer.

Funding

This study was supported by the National Institutes of Health [R21AA025723, R01HL136345, and R01AA028527]; NSF-CASIS (National Science Foundation-Center for the Advancement of Science in Space) [CBET 1926387]; the Center for Pediatric Technology at Emory University; and Georgia Institute of Technology; and Imagine, Innovate and Impact (I3) Funds from the Emory School of Medicine and through the Georgia CTSA NIH award [UL1-TR002378].

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Authors and Affiliations

  1. Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA

    Rui Liu, Lawrence C. Armand & Chunhui Xu

  2. Department of Pediatrics, The Third **angya Hospital of Central South University, Changsha, 410013, Hunan, China

    Rui Liu

  3. School of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA

    Fangxu Sun & Ronghu Wu

  4. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30322, USA

    Chunhui Xu

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Contributions

R.L., F.S., R.W., and C.X. designed experiments. R.L. and F.S. performed experiments. R.L., F.S., and L.C.A. analyzed data. R.L., F.S., L.C.A., R.W., and C.X. wrote the manuscript. All authors contributed to the discussion of results and editing and final approval of the manuscript.

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Correspondence to Chunhui Xu.

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Liu, R., Sun, F., Armand, L.C. et al. Chronic Ethanol Exposure Induces Deleterious Changes in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells. Stem Cell Rev and Rep 17, 2314–2331 (2021). https://doi.org/10.1007/s12015-021-10267-y

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