Gatheridge, M. A. et al. Identifying non–Duchenne muscular dystrophy–positive and false negative results in prior Duchenne muscular dystrophy newborn screening programs: a review. JAMA Neurol. 73, 111 (2016).
Google Scholar
Rahimov, F. & Kunkel, L. M. Cellular and molecular mechanisms underlying muscular dystrophy. J. Cell Biol. 201, 499–510 (2013).
Google Scholar
Bladen, C. L. et al. The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum. Mutat. 36, 395–402 (2015).
Google Scholar
Gao, Q. Q. & McNally, E. M. The dystrophin complex: structure, function, and implications for therapy. Compr. Physiol. 5, 1223–1239 (2015).
Google Scholar
Deconinck, N. & Dan, B. Pathophysiology of Duchenne muscular dystrophy: current hypotheses. Pediatr. Neurol. 36, 1–7 (2007).
Google Scholar
Spurney, C. F. Cardiomyopathy of Duchenne muscular dystrophy: current understanding and future directions. Muscle Nerve 44, 8–19 (2011).
Google Scholar
D’Amario, D. et al. A current approach to heart failure in Duchenne muscular dystrophy. Heart 103, 1770–1779 (2017).
Google Scholar
Mourkioti, F. et al. Role of telomere dysfunction in cardiac failure in Duchenne muscular dystrophy. Nat. Cell Biol. 15, 895–904 (2013).
Google Scholar
Chang, A. C. Y. et al. Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy. Proc. Natl Acad. Sci. USA 113, 13120–13125 (2016).
Google Scholar
Kamdar, F. & Garry, D. J. Dystrophin-deficient cardiomyopathy. J. Am. Coll. Cardiol. 67, 2533–2546 (2016).
Google Scholar
Adorisio, R. et al. Duchenne dilated cardiomyopathy: cardiac management from prevention to advanced cardiovascular therapies. J. Clin. Med. 9, 3186 (2020).
Google Scholar
Khairallah, R. J. et al. Microtubules underlie dysfunction in Duchenne muscular dystrophy. Sci. Signal. 5, ra56 (2012).
Google Scholar
Birnkrant, D. J. et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 17, 347–361 (2018).
Google Scholar
Cheeran, D. et al. Predictors of death in adults with Duchenne muscular dystrophy-associated cardiomyopathy. J. Am. Heart Assoc. 6, e006340 (2021).
McNally, E. M. et al. Contemporary cardiac issues in Duchenne muscular dystrophy. Circulation 131, 1590–1598 (2015).
Google Scholar
Spurney, C. et al. Cooperative international neuromuscular research group Duchenne natural history study demonstrates insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular dystrophy. Muscle Nerve 50, 250–256 (2014).
Google Scholar
Gayi, E. et al. Repurposing the selective oestrogen receptor modulator tamoxifen for the treatment of Duchenne muscular dystrophy. Chimia 72, 238–240 (2018).
Google Scholar
Dorchies, O. M. et al. The anticancer drug Tamoxifen counteracts the pathology in a mouse model of Duchenne muscular dystrophy. Am. J. Pathol. 182, 485–504 (2013).
Google Scholar
Arnott, J., Martinkovich, S., Planey, S. L. & Shah, D. Selective estrogen receptor modulators: tissue specificity and clinical utility. Clin. Interv. Aging 1437, https://doi.org/10.2147/CIA.S66690 (2014).
Mahmoodzadeh, S. et al. Estrogen receptor alpha up‐regulation and redistribution in human heart failure. FASEB J. 20, 926–934 (2006).
Google Scholar
Kallen, A. N. & Pal, L. Cardiovascular disease and ovarian function. Curr. Opin. Obstet. Gynecol. 23, 258–267 (2011).
Google Scholar
Yang, X.-P. & Reckelhoff, J. F. Estrogen, hormonal replacement therapy and cardiovascular disease. Curr. Opin. Nephrol. Hypertens. 20, 133–138 (2011).
Google Scholar
Koot, R. W., Amelink, G. J., Blankenstein, M. A. & Bär, P. R. Tamoxifen and oestrogen both protect the rat muscle against physiological damage. J. Steroid Biochem. Mol. Biol. 40, 689–IN10 (1991).
Google Scholar
Custódio, JoséB. A., Dinis, T. C. P., Almeida, L. M. & Madeira, V. M. C. Tamoxifen and hydroxytamoxifen as intramembraneous inhibitors of lipid peroxidation. Evidence for peroxyl radical scavenging activity. Biochem. Pharmacol. 47, 1989–1998 (1994).
Google Scholar
Dodds, M. L., Kargacin, M. E. & Kargacin, G. J. Effects of anti-oestrogens and β-estradiol on calcium uptake by cardiac sarcoplasmic reticulum. Br. J. Pharmacol. 132, 1374–1382 (2001).
Google Scholar
Patel, B. M. & Desai, V. J. Beneficial role of tamoxifen in experimentally induced cardiac hypertrophy. Pharmacol. Rep. 66, 264–272 (2014).
Google Scholar
Nagy, S. et al. Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial. Trials 20, 637 (2019).
Google Scholar
Chang, A. C. Y. et al. Telomere shortening is a hallmark of genetic cardiomyopathies. Proc. Natl Acad. Sci. USA 115, 9276–9281 (2018).
Google Scholar
Zhang, J. Z. et al. A human iPSC double-reporter system enables purification of cardiac lineage subpopulations with distinct function and drug response profiles. Cell Stem Cell 24, 802–811.e5 (2019).
Google Scholar
Wu, H. et al. Modelling diastolic dysfunction in induced pluripotent stem cell-derived cardiomyocytes from hypertrophic cardiomyopathy patients. Eur. Heart J. 40, 3685–3695 (2019).
Google Scholar
Chang, A. C. Y. et al. Increased tissue stiffness triggers contractile dysfunction and telomere shortening in dystrophic cardiomyocytes. Stem Cell Rep. 16, 1–13 (2021).
Yang, X., Pabon, L. & Murry, C. E. Engineering adolescence: maturation of human pluripotent stem cell–derived cardiomyocytes. Circ. Res. 114, 511–523 (2014).
Google Scholar
Knöll, R., Buyandelger, B. & Lab, M. The sarcomeric Z-disc and Z-discopathies. J. Biomed. Biotechnol. 2011, 1–12 (2011).
Louch, W. E. Methods in cardiomyocyte isolation, culture, and gene transfer. J. Mol. Cell. Cardiol. 51, 288–298 (2011).
Google Scholar
da Rocha, A. M. et al. hiPSC-CM monolayer maturation state determines drug responsiveness in high throughput pro-arrhythmia screen. Sci. Rep. 7, 13834 (2017).
Google Scholar
Madl, C. M., Flaig, I. A., Holbrook, C. A., Wang, Y. X. & Blau, H. M. Biophysical matrix cues from the regenerating niche direct muscle stem cell fate in engineered microenvironments. Biomaterials 275, 120973 (2021).
Google Scholar
Paik, D. T., Chandy, M. & Wu, J. C. Patient and disease-specific induced pluripotent stem cells for discovery of personalized cardiovascular drugs and therapeutics. Pharmacol. Rev. 72, 320–342 (2020).
Google Scholar
Ribeiro, A. J. S. et al. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc. Natl Acad. Sci. USA 112, 12705–12710 (2015).
Google Scholar
Schroer, A., Pardon, G., Castillo, E., Blair, C. & Pruitt, B. Engineering hiPSC cardiomyocyte in vitro model systems for functional and structural assessment. Prog. Biophys. Mol. Biol. 144, 3–15 (2019).
Google Scholar
Huebsch, N. et al. Automated video-based analysis of contractility and calcium flux in human-induced pluripotent stem cell-derived cardiomyocytes cultured over different spatial scales. Tissue Eng. Part C. Methods 21, 467–479 (2015).
Google Scholar
Mathur, A. et al. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci. Rep. 5, 8883 (2015).
Google Scholar
Sakamoto, T. et al. A critical role for estrogen-related receptor signaling in cardiac maturation. Circ. Res. 126, 1685–1702 (2020).
Google Scholar
Guan, X. et al. Dystrophin-deficient cardiomyocytes derived from human urine: new biologic reagents for drug discovery. Stem Cell Res. 12, 467–480 (2014).
Google Scholar
Pioner, J. M. et al. Absence of full-length dystrophin impairs normal maturation and contraction of cardiomyocytes derived from human-induced pluripotent stem cells. Cardiovasc. Res. 116, 368–382 (2020).
Google Scholar
Dick, E. et al. Two new protocols to enhance the production and isolation of human induced pluripotent stem cell lines. Stem Cell Res. 6, 158–167 (2011).
Google Scholar
Dick, E. et al. Exon skipping and gene transfer restore dystrophin expression in human induced pluripotent stem cells-cardiomyocytes harboring DMD mutations. Stem Cells Dev. 22, 2714–2724 (2013).
Google Scholar
Kaspar, R. W. et al. Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in Becker muscular dystrophy. Circ. Cardiovasc. Genet. 2, 544–551 (2009).
Google Scholar
Austin, R. C., Howard, P. L., D’Souza, V. N., Klamut, H. J. & Ray, P. N. Cloning and characterization of alternatively spliced isoforms of Dp71. Hum. Mol. Genet. 4, 1475–1483 (1995).
Google Scholar
Jelinkova, S. et al. DMD pluripotent stem cell derived cardiac cells recapitulate in vitro human cardiac pathophysiology. Front. Bioeng. Biotechnol. 8, 535 (2020).
Google Scholar
Barresi, R. & Campbell, K. P. Dystroglycan: from biosynthesis to pathogenesis of human disease. J. Cell Sci. 119, 199–207 (2006).
Google Scholar
Kamdar, F. et al. Stem cell-derived cardiomyocytes and beta-adrenergic receptor blockade in Duchenne muscular dystrophy cardiomyopathy. J. Am. Coll. Cardiol. 75, 1159–1174 (2020).
Google Scholar
Ropero, A. B. et al. Heart estrogen receptor alpha: distinct membrane and nuclear distribution patterns and regulation by estrogen. J. Mol. Cell. Cardiol. 41, 496–510 (2006).
Google Scholar
Lizotte, E., Grandy, S. A., Tremblay, A., Allen, B. G. & Fiset, C. Expression, distribution and regulation of sex steroid hormone receptors in mouse heart. Cell. Physiol. Biochem. 23, 075–086 (2009).
Google Scholar
Yaşar, P., Ayaz, G., User, S. D., Güpür, G. & Muyan, M. Molecular mechanism of estrogen–estrogen receptor signaling. Reprod. Med. Biol. 16, 4–20 (2016).
Google Scholar
Jonsson, M. K. B., Wang, Q.-D. & Becker, B. Impedance-based detection of beating rhythm and proarrhythmic effects of compounds on stem cell-derived cardiomyocytes. ASSAY Drug Dev. Technol. 9, 589–599 (2011).
Google Scholar
Lemoine, M. D. et al. Human induced pluripotent stem cell–derived engineered heart tissue as a sensitive test system for QT prolongation and arrhythmic triggers. Circ. Arrhythm. Electrophysiol. 11, e006035 (2018).
Navarrete, E. G. et al. Screening drug-induced arrhythmia using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation 128, S3–S13 (2013).
Google Scholar
Weiss, J. N., Garfinkel, A., Karagueuzian, H. S., Chen, P.-S. & Qu, Z. Early afterdepolarizations and cardiac arrhythmias. Heart Rhythm 7, 1891–1899 (2010).
Google Scholar
Prosser, B. L., Ward, C. W. & Lederer, W. J. X-ROS signaling: rapid mechano-chemo transduction in heart. Science 333, 1440–1445 (2011).
Google Scholar
Bostick, B., Yue, Y. & Duan, D. Gender influences cardiac function in the mdx model of Duchenne cardiomyopathy. Muscle Nerve 42, 600–603 (2010).
Google Scholar
Sacco, A. et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell 143, 1059–1071 (2010).
Google Scholar
Jordan, V. C. Tamoxifen: a most unlikely pioneering medicine. Nat. Rev. Drug Discov. 2, 205–213 (2003).
Google Scholar
Cui, J., Shen, Y. & Li, R. Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends Mol. Med. 19, 197–209 (2013).
Google Scholar
Grumbach, M. M. & Auchus, R. J. Estrogen: consequences and implications of human mutations in synthesis and action. J. Clin. Endocrinol. Metab. 84, 4677–4694 (1999).
Google Scholar
Yao, J., Deng, K., Huang, J., Zeng, R. & Zuo, J. Progress in the understanding of the mechanism of tamoxifen resistance in breast cancer. Front. Pharmacol. 11, 592912 (2020).
Google Scholar
Brzozowski, A. M. et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753–758 (1997).
Google Scholar
Shiau, A. K. et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95, 927–937 (1998).
Google Scholar
Meyer, M. R., Haas, E., Prossnitz, E. R. & Barton, M. Non-genomic regulation of vascular cell function and growth by estrogen. Mol. Cell. Endocrinol. 308, 9–16 (2009).
Google Scholar
Filardo, E. J., Quinn, J. A., Frackelton, A. R. & Bland, K. I. Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol. Endocrinol. 16, 70–84 (2002).
Google Scholar
Jiang, C. et al. Effect of 17β‐oestradiol on contraction, Ca2+ current and intracellular free Ca2+ in guinea‐pig isolated cardiac myocytes. Br. J. Pharmacol. 106, 739–745 (1992).
Google Scholar
Nordenskjöld, B. et al. Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: results from a randomized trial. JNCI J. Natl Cancer Inst. 97, 1609–1610 (2005).
Google Scholar
Gylling, H. et al. Tamoxifen and toremifene lower serum cholesterol by inhibition of delta 8-cholesterol conversion to lathosterol in women with breast cancer. J. Clin. Oncol. 13, 2900–2905 (1995).
Google Scholar
Holleran, A. L., Lindenthal, B., Aldaghlas, T. A. & Kelleher, J. K. Effect of tamoxifen on cholesterol synthesis in HepG2 cells and cultured rat hepatocytes. Metabolism 47, 1504–1513 (1998).
Google Scholar
Medina, P. de. et al. Tamoxifen is a potent inhibitor of cholesterol esterification and prevents the formation of foam cells. J. Pharmacol. Exp. Ther. 308, 1165–1173 (2004).
Google Scholar
Love, R. R. et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann. Intern. Med. 115, 860 (1991).
Google Scholar
Lian, X. et al. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc. Natl Acad. Sci. USA 109, E1848–E1857 (2012).
Google Scholar
Burridge, P. W. et al. Chemically defined generation of human cardiomyocytes. Nat. Methods 11, 855–860 (2014).
Google Scholar
Tohyama, S. et al. Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell 12, 127–137 (2013).
Google Scholar

