Skip to main content

Advertisement

Log in

Cardiac Remodelling Following Cancer Therapy: A Review

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Cardiac remodelling is characterized by abnormal changes in the function and morphological properties such as diameter, mass, normal diameter of cavities, heart shape, fibrosis, thickening of vessels and heart layers, cardiomyopathy, infiltration of inflammatory cells, and some others. These damages are associated with damage to systolic and diastolic abnormalities, damage to ventricular function, and vascular remodelling, which may lead to heart failure and death. Exposure of the heart to radiation or anti-cancer drugs including chemotherapy drugs such as doxorubicin, receptor tyrosine kinase inhibitors (RTKIs) such as imatinib, and immune checkpoint inhibitors (ICIs) can induce several abnormal changes in the heart structure and function through the induction of inflammation and fibrosis, vascular remodelling, hypertrophy, and some others. This review aims to explain the basic mechanisms behind cardiac remodelling following cancer therapy by different anti-cancer modalities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D. M., Piñeros, M., Znaor, A., et al. (2021). Cancer statistics for the year 2020: An overview. International Journal of Cancer, 149(4), 778–789.

    Article  CAS  Google Scholar 

  2. Liu, Y.-Q., Wang, X.-L., He, D.-H., & Cheng, Y.-X. (2021). Protection against chemotherapy-and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals. Phytomedicine, 80, 153402.

    Article  CAS  PubMed  Google Scholar 

  3. Minami, M., Matsumoto, S., & Horiuchi, H. (2010). Cardiovascular side-effects of modern cancer therapy. Circulation Journal, 2010, 1008100855.

    Google Scholar 

  4. Perez, I. E., Taveras Alam, S., Hernandez, G. A., & Sancassani, R. (2019). Cancer therapy-related cardiac dysfunction: An overview for the clinician. Clinical Medicine Insights: Cardiology, 13, 1179546819866445.

    PubMed  PubMed Central  Google Scholar 

  5. Chen, D.-Y., Huang, W.-K., Wu, V.C.-C., Chang, W.-C., Chen, J.-S., Chuang, C.-K., et al. (2020). Cardiovascular toxicity of immune checkpoint inhibitors in cancer patients: A review when cardiology meets immuno-oncology. Journal of the Formosan Medical Association., 119(10), 1461–75.

    Article  CAS  PubMed  Google Scholar 

  6. Zagar, T. M., Cardinale, D. M., & Marks, L. B. (2016). Breast cancer therapy-associated cardiovascular disease. Nature Reviews Clinical Oncology., 13(3), 172–184.

    Article  CAS  PubMed  Google Scholar 

  7. Boopathi, E., & Thangavel, C. (2021). Dark side of cancer therapy: Cancer Treatment-induced cardiopulmonary inflammation, fibrosis, and immune modulation. International Journal of Molecular Sciences, 22(18), 10126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Du, X. L., Xia, R., Liu, C. C., Cormier, J. N., Xing, Y., Hardy, D., et al. (2009). Cardiac toxicity associated with anthracycline-containing chemotherapy in older women with breast cancer. Cancer, 115(22), 5296–5308.

    Article  PubMed  Google Scholar 

  9. Cardinale, D., Colombo, A., Lamantia, G., Colombo, N., Civelli, M., De Giacomi, G., et al. (2010). Anthracycline-induced cardiomyopathy: Clinical relevance and response to pharmacologic therapy. Journal of the American College of Cardiology, 55(3), 213–220.

    Article  CAS  PubMed  Google Scholar 

  10. Grover, S. P., Hisada, Y. M., Kasthuri, R. S., Reeves, B. N., & Mackman, N. (2021). Cancer therapy-associated thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 41(4), 1291–1305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Galvano, A., Guarini, A., Iacono, F., Castiglia, M., Rizzo, S., Tarantini, L., et al. (2019). An update on the conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting TKI-based therapy. Expert Opinion on Drug Safety., 18(6), 485–496.

    Article  PubMed  Google Scholar 

  12. Azevedo, P. S., Polegato, B. F., Minicucci, M. F., Paiva, S. A. R., & Zornoff, L. A. M. (2016). Cardiac remodeling: Concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arquivos brasileiros de cardiologia., 106(1), 62–69. https://doi.org/10.5935/abc.20160005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hochman, J. S., & Bulkley, B. H. (1982). Expansion of acute myocardial infarction: An experimental study. Circulation, 65(7), 1446–1450.

    Article  CAS  PubMed  Google Scholar 

  14. Liu, L., & Eisen, H. J. (2014). Epidemiology of heart failure and scope of the problem. Cardiology Clinics, 32(1), 1–8. https://doi.org/10.1016/j.ccl.2013.09.009

    Article  CAS  PubMed  Google Scholar 

  15. Dorn, G. W., 2nd. (2009). Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling. Cardiovascular Research, 81(3), 465–473. https://doi.org/10.1093/cvr/cvn243

    Article  CAS  PubMed  Google Scholar 

  16. Yang, R., Tan, C., & Najafi, M. (2021). Cardiac inflammation and fibrosis following chemo/radiation therapy: Mechanisms and therapeutic agents. Inflammopharmacology. https://doi.org/10.1007/s10787-021-00894-9

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lu, M., Qin, X., Yao, J., Yang, Y., Zhao, M., & Sun, L. (2020). Th17/Treg imbalance modulates rat myocardial fibrosis and heart failure by regulating LOX expression. Acta Physiologica, 230(3), e13537.

    Article  CAS  PubMed  Google Scholar 

  18. Shao, P.-P., Liu, C.-J., Xu, Q., Zhang, B., Li, S.-H., Wu, Y., et al. (2018). Eplerenone reverses cardiac fibrosis via the suppression of tregs by inhibition of Kv1. 3 channel. Frontiers in Physiology, 9, 899.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fung, T. H., Yang, K. Y., & Lui, K. O. (2020). An emerging role of regulatory T-cells in cardiovascular repair and regeneration. Theranostics, 10(20), 8924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Frieler, R. A., & Mortensen, R. M. (2015). Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling. Circulation, 131(11), 1019–1030. https://doi.org/10.1161/circulationaha.114.008788

    Article  PubMed  PubMed Central  Google Scholar 

  21. Xiao, H., Li, H., Wang, J.-J., Zhang, J.-S., Shen, J., An, X.-B., et al. (2018). IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. European Heart Journal, 39(1), 60–69.

    Article  CAS  PubMed  Google Scholar 

  22. Fu, X., Tang, J., Wen, P., Huang, Z., & Najafi, M. (2021). Redox interactions-induced cardiac toxicity in cancer therapy. Archives of Biochemistry and Biophysics, 708, 108952. https://doi.org/10.1016/j.abb.2021.108952

    Article  CAS  PubMed  Google Scholar 

  23. Hori, M., & Nishida, K. (2009). Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovascular Research, 81(3), 457–464.

    Article  CAS  PubMed  Google Scholar 

  24. Briasoulis, A., Androulakis, E., Christophides, T., & Tousoulis, D. (2016). The role of inflammation and cell death in the pathogenesis, progression and treatment of heart failure. Heart Failure Reviews, 21(2), 169–176.

    Article  CAS  PubMed  Google Scholar 

  25. Grover, S., Lou, P., Bradbrook, C., Cheong, K., Kotasek, D., Leong, D., et al. (2015). Early and late changes in markers of aortic stiffness with breast cancer therapy. Internal Medicine Journal, 45(2), 140–147.

    Article  CAS  PubMed  Google Scholar 

  26. Raghunathan, D., Khilji, M. I., Hassan, S. A., & Yusuf, S. W. (2017). Radiation-induced cardiovascular disease. Current Atherosclerosis Reports, 19(5), 22.

    Article  PubMed  Google Scholar 

  27. Yusuf, S. W., Venkatesulu, B. P., Mahadevan, L. S., & Krishnan, S. (2017). Radiation-induced cardiovascular disease: A clinical perspective. Frontiers in Cardiovascular Medicine., 4, 66.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Oun, R., & Rowan, E. (2017). Cisplatin induced arrhythmia; electrolyte imbalance or disturbance of the SA node? European Journal of Pharmacology, 811, 125–128.

    Article  CAS  PubMed  Google Scholar 

  29. Patanè, S. (2014). Cardiotoxicity: Cisplatin and long-term cancer survivors. International Journal of Cardiology., 175(1), 201–202.

    Article  PubMed  Google Scholar 

  30. Hilmi, M., Ederhy, S., Waintraub, X., Funck-Brentano, C., Cohen, A., Vozy, A., et al. (2020). Cardiotoxicity associated with gemcitabine: Literature review and a pharmacovigilance study. Pharmaceuticals, 13(10), 325. https://doi.org/10.3390/ph13100325

    Article  CAS  PubMed Central  Google Scholar 

  31. Sara, J. D., Kaur, J., Khodadadi, R., Rehman, M., Lobo, R., Chakrabarti, S., et al. (2018). 5-fluorouracil and cardiotoxicity: A review. Therapeutic Advances in Medical Oncology, 10, 1758835918780140. https://doi.org/10.1177/1758835918780140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mizia-Stec, K., Gościńska, A., Mizia, M., Haberka, M., Chmiel, A., Poborski, W., et al. (2013). Anthracycline chemotherapy impairs the structure and diastolic function of the left ventricle and induces negative arterial remodelling. Kardiologia Polska, 71(7), 681–690.

    Article  PubMed  Google Scholar 

  33. Lupón, J., Gavidia-Bovadilla, G., Ferrer, E., de Antonio, M., Perera-Lluna, A., López-Ayerbe, J., et al. (2018). Dynamic trajectories of left ventricular ejection fraction in heart failure. Journal of the American College of Cardiology., 72(6), 591–601.

    Article  PubMed  Google Scholar 

  34. Kumar, S., Marfatia, R., Tannenbaum, S., Yang, C., & Avelar, E. (2012). Doxorubicin-induced cardiomyopathy 17 years after chemotherapy. Texas Heart Institute Journal., 39(3), 424.

    PubMed  PubMed Central  Google Scholar 

  35. Trapani, D., Zagami, P., Nicolò, E., Pravettoni, G., & Curigliano, G. (2020). Management of cardiac toxicity induced by chemotherapy. Journal of Clinical Medicine., 9(9), 2885.

    Article  CAS  PubMed Central  Google Scholar 

  36. Hu, J.-R., Florido, R., Lipson, E. J., Naidoo, J., Ardehali, R., Tocchetti, C. G., et al. (2019). Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovascular Research., 115(5), 854–868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wu, Q.-Q., Xiao, Y., Yuan, Y., Ma, Z.-G., Liao, H.-H., Liu, C., et al. (2017). Mechanisms contributing to cardiac remodelling. Clinical Science., 131(18), 2319–2345.

    Article  CAS  PubMed  Google Scholar 

  38. Mortezaee, K., & Najafi, M. (2021). Immune system in cancer radiotherapy: Resistance mechanisms and therapy perspectives. Critical Reviews in Oncology/Hematology., 157, 103180.

    Article  PubMed  Google Scholar 

  39. Chitturi, K. R., Araujo-Gutierrez, R., McLean, E. T., Xu, J., Bhimaraj, A., Guha, A., et al. (2019). Cardiotoxicity of immune checkpoint inhibitors in patients with lung cancer. Journal of Cardiac Failure, 25(8), S50. https://doi.org/10.1016/j.cardfail.2019.07.141

    Article  Google Scholar 

  40. Michel, L., Totzeck, M., Lehmann, L., & Finke, D. (2020). Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system. Herz, 45(7), 645–651. https://doi.org/10.1007/s00059-020-04954-8

    Article  PubMed  Google Scholar 

  41. Ranpura, V., Hapani, S., Chuang, J., & Wu, S. (2010). Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: A meta-analysis of randomized controlled trials. Acta Oncologica, 49(3), 287–297.

    Article  CAS  PubMed  Google Scholar 

  42. Economopoulou, P., Kotsakis, A., Kapiris, I., & Kentepozidis, N. (2015). Cancer therapy and cardiovascular risk: Focus on bevacizumab. Cancer Management and Research, 7, 133.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ghatalia, P., Morgan, C. J., Je, Y., Nguyen, P. L., Trinh, Q.-D., Choueiri, T. K., et al. (2015). Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Critical Reviews in Oncology/Hematology, 94(2), 228–237.

    Article  PubMed  Google Scholar 

  44. Khakoo, A. Y., Kassiotis, C. M., Tannir, N., Plana, J. C., Halushka, M., Bickford, C., et al. (2008). Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer: Interdisciplinary International Journal of the American Cancer Society., 112(11), 2500–2508.

    Article  CAS  Google Scholar 

  45. Pentassuglia, L., Graf, M., Lane, H., Kuramochi, Y., Cote, G., Timolati, F., et al. (2009). Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes. Experimental Cell Research., 315(7), 1302–1312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Farhood, B., Goradel, N. H., Mortezaee, K., Khanlarkhani, N., Salehi, E., Nashtaei, M. S., et al. (2019). Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation. Journal of Cell Communication and Signaling., 13(1), 3–16. https://doi.org/10.1007/s12079-018-0473-3

    Article  PubMed  Google Scholar 

  47. Harel, S., Mayaki, D., Sanchez, V., & Hussain, S. N. (2017). NOX2, NOX4, and mitochondrial-derived reactive oxygen species contribute to angiopoietin-1 signaling and angiogenic responses in endothelial cells. Vascular Pharmacology, 92, 22–32.

    Article  CAS  PubMed  Google Scholar 

  48. Navarro-Yepes, J., Burns, M., Anandhan, A., Khalimonchuk, O., Del Razo, L. M., Quintanilla-Vega, B., et al. (2014). Oxidative stress, redox signaling, and autophagy: Cell death versus survival. Antioxidants & Redox Signaling., 21(1), 66–85.

    Article  CAS  Google Scholar 

  49. Livingston, K., Schlaak, R. A., Puckett, L. L., & Bergom, C. (2020). The role of mitochondrial dysfunction in radiation-induced heart disease: From bench to bedside. Frontiers in Cardiovascular Medicine., 7, 20. https://doi.org/10.3389/fcvm.2020.00020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Panganiban, R. A., Mungunsukh, O., & Day, R. M. (2013). X-irradiation induces ER stress, apoptosis, and senescence in pulmonary artery endothelial cells. International Journal of Radiation Biology, 89(8), 656–667. https://doi.org/10.3109/09553002.2012.711502

    Article  CAS  PubMed  Google Scholar 

  51. Palaskas, N., Patel, A., & Yusuf, S. W. (2019). Radiation and cardiovascular disease. Annals of Translational Medicine S371.

  52. Wang, B., Wang, H., Zhang, M., Ji, R., Wei, J., Xin, Y., et al. (2020). Radiation-induced myocardial fibrosis: Mechanisms underlying its pathogenesis and therapeutic strategies. Journal of Cellular and Molecular Medicine, 24(14), 7717–7729.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Arola, O. J., Saraste, A., Pulkki, K., Kallajoki, M., Parvinen, M., & Voipio-Pulkki, L.-M. (2000). Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Research, 60(7), 1789–1792.

    CAS  PubMed  Google Scholar 

  54. Dhingra, R., Margulets, V., Chowdhury, S. R., Thliveris, J., Jassal, D., Fernyhough, P., et al. (2014). Bnip3 mediates doxorubicin-induced cardiac myocyte necrosis and mortality through changes in mitochondrial signaling. Proceedings of the National Academy of Sciences., 111(51), E5537–E5544.

    Article  CAS  Google Scholar 

  55. Ashrafizadeh, M., Farhood, B., Eleojo Musa, A., Taeb, S., & Najafi, M. (2020). Damage-associated molecular patterns in tumor radiotherapy. International Immunopharmacology., 86, 106761. https://doi.org/10.1016/j.intimp.2020.106761

    Article  CAS  PubMed  Google Scholar 

  56. Yahyapour, R., Motevaseli, E., Rezaeyan, A., Abdollahi, H., Farhood, B., Cheki, M., et al. (2018). Mechanisms of radiation bystander and non-targeted effects: Implications to radiation carcinogenesis and radiotherapy. Current Radiopharmaceuticals, 11(1), 34–45. https://doi.org/10.2174/1874471011666171229123130

    Article  CAS  PubMed  Google Scholar 

  57. Farhood, B., Ashrafizadeh, M., Hoseini-Ghahfarokhi, M., Afrashi, S., Musa, A. E., & Najafi, M. (2020). Targeting of cellular redox metabolism for mitigation of radiation injury. Life Sciences., 250, 117570.

    Article  CAS  PubMed  Google Scholar 

  58. Wijerathne, H., Langston, J., Yang, Q., Sun, S., Miyamoto, C., Kilpatrick, L. E., et al. (2021). Mechanisms of radiation-induced endothelium damage: Emerging models and technologies. Radiotherapy and Oncology., 158, 21–32.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Chiabrando, J. G., Bonaventura, A., Vecchié, A., Wohlford, G. F., Mauro, A. G., Jordan, J. H., et al. (2020). Management of acute and recurrent pericarditis: JACC state-of-the-art review. Journal of the American College of Cardiology., 75(1), 76–92. https://doi.org/10.1016/j.jacc.2019.11.021

    Article  CAS  PubMed  Google Scholar 

  60. Chang, A., Nasti, T. H., Khan, M. K., Parashar, S., Kaufman, J. L., Boise, L. H., et al. (2018). Myocarditis with radiotherapy and immunotherapy in multiple myeloma. Journal of Oncology Practice., 14(9), 561–564. https://doi.org/10.1200/JOP.18.00208

    Article  PubMed  Google Scholar 

  61. Tada, Y., & Suzuki, J.-I. (2016). Oxidative stress and myocarditis. Current Pharmaceutical Design., 22(4), 450–71.

    Article  CAS  PubMed  Google Scholar 

  62. Bagchi, A. K., Malik, A., Akolkar, G., Jassal, D. S., & Singal, P. K. (2021). Endoplasmic reticulum stress promotes iNOS/NO and influences inflammation in the development of doxorubicin-induced cardiomyopathy. Antioxidants., 10(12), 1897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mortezaee, K., Najafi, M., Farhood, B., Ahmadi, A., Shabeeb, D., & Musa, A. E. (2019). NF-κB targeting for overcoming tumor resistance and normal tissues toxicity. Journal of Cellular Physiology., 234(10), 17187–17204. https://doi.org/10.1002/jcp.28504

    Article  CAS  PubMed  Google Scholar 

  64. Mahmood, S. S., Fradley, M. G., Cohen, J. V., Nohria, A., Reynolds, K. L., Heinzerling, L. M., et al. (2018). Myocarditis in patients treated with immune checkpoint inhibitors. Journal of the American College of Cardiology., 71(16), 1755–1764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Johnson, D. B., Balko, J. M., Compton, M. L., Chalkias, S., Gorham, J., Xu, Y., et al. (2016). Fulminant myocarditis with combination immune checkpoint blockade. New England Journal of Medicine., 375(18), 1749–1755.

    Article  PubMed  CAS  Google Scholar 

  66. Ji, C., Roy, M. D., Golas, J., Vitsky, A., Ram, S., Kumpf, S. W., et al. (2019). Myocarditis in cynomolgus monkeys following treatment with immune checkpoint inhibitors. Clinical Cancer Research., 25(15), 4735–4748.

    Article  CAS  PubMed  Google Scholar 

  67. Berner, A., Sharma, A., Agarwal, S., Al-Sam, S., & Nathan, P. (2018). Fatal autoimmune myocarditis with anti–PD-L1 and tyrosine kinase inhibitor therapy for renal cell cancer. European Journal of Cancer., 101, 287–290.

    Article  CAS  PubMed  Google Scholar 

  68. Burke, M. J., Walmsley, R., Munsey, T. S., & Smith, A. J. (2019). Receptor tyrosine kinase inhibitors cause dysfunction in adult rat cardiac fibroblasts in vitro. Toxicology in Vitro., 58, 178–186.

    Article  CAS  PubMed  Google Scholar 

  69. Rocca, C., De Francesco, E. M., Pasqua, T., Granieri, M. C., De Bartolo, A., Gallo Cantafio, M. E., et al. (2022). Mitochondrial determinants of anti-cancer drug-induced cardiotoxicity. Biomedicines., 10(3), 520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Truell, J. S., Fishbein, M. C., & Figlin, R. (2005). Myocarditis temporally related to the use of gefitinib (Iressa). Archives of Pathology & Laboratory Medicine., 129(8), 1044–1046.

    Article  Google Scholar 

  71. Rezaeyan, A., Haddadi, G. H., Hosseinzadeh, M., Moradi, M., & Najafi, M. (2016). Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue. Journal of Medical Physics., 41(3), 182–191. https://doi.org/10.4103/0971-6203.189482

    Article  PubMed  PubMed Central  Google Scholar 

  72. Najafi, M., Shirazi, A., Motevaseli, E., Rezaeyan, A. H., Salajegheh, A., & Rezapoor, S. (2017). Melatonin as an anti-inflammatory agent in radiotherapy. Inflammopharmacology, 25(4), 403–413. https://doi.org/10.1007/s10787-017-0332-5

    Article  CAS  PubMed  Google Scholar 

  73. Najafi, M., Motevaseli, E., Geraily, G., Norouzi, F., Heidari, M., & Rezapoor, S. (2017). The melatonin immunomodulatory actions in radiotherapy. Biophysical Reviews, 9(2), 139–148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gürses, İ, Özeren, M., Serin, M., Yücel, N., & Erkal, H. Ş. (2014). Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model. Pathology—Research and Practice, 210(12), 863–871. https://doi.org/10.1016/j.prp.2014.08.006

    Article  CAS  PubMed  Google Scholar 

  75. Farhood, B., Aliasgharzadeh, A., Amini, P., Saffar, H., Motevaseli, E., Rezapoor, S., et al. (2019). Radiation-induced dual oxidase upregulation in rat heart tissues: Protective effect of melatonin. Medicina, 55(7), 317. https://doi.org/10.3390/medicina55070317

    Article  PubMed Central  Google Scholar 

  76. Dhingra, A., Jayas, R., Afshar, P., Guberman, M., Maddaford, G., Gerstein, J., et al. (2017). Ellagic acid antagonizes Bnip3-mediated mitochondrial injury and necrotic cell death of cardiac myocytes. Free Radical Biology and Medicine, 112, 411–422. https://doi.org/10.1016/j.freeradbiomed.2017.08.010

    Article  CAS  PubMed  Google Scholar 

  77. Gurses, I., Ozeren, M., Serin, M., Yucel, N., & Erkal, H. S. (2018). Histopathological efficiency of amifostine in radiationinduced heart disease in rats. Bratislavske Lekarske Listy, 119(1), 54–59. https://doi.org/10.4149/bll_2018_011

    Article  CAS  PubMed  Google Scholar 

  78. Kolivand, S., Amini, P., Saffar, H., Rezapoor, S., Motevaseli, E., Najafi, M., et al. (2019). Evaluating the radioprotective effect of curcumin on rat’s heart tissues. Current Radiopharmaceuticals, 12(1), 23–28. https://doi.org/10.2174/1874471011666180831101459

    Article  CAS  PubMed  Google Scholar 

  79. Yahyapour, R., Amini, P., Saffar, H., Rezapoor, S., Motevaseli, E., Cheki, M., et al. (2018). Metformin protects against radiation-induced heart injury and attenuates the upregulation of dual oxidase genes following Rat’s chest irradiation. International Journal of Molecular and Cellular Medicine, 7(3), 193–202. https://doi.org/10.22088/IJMCM.BUMS.7.3.193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kolivand, S., Amini, P., Saffar, H., Rezapoor, S., Najafi, M., Motevaseli, E., et al. (2019). Selenium-L-methionine modulates radiation injury and Duox1 and Duox2 upregulation in rat’s heart tissues. Journal of Cardiovascular and Thoracic Research, 11(2), 121–126. https://doi.org/10.15171/jcvtr.2019.21

    Article  PubMed  PubMed Central  Google Scholar 

  81. Yang, C.-M., Lee, I.-T., Hsu, R.-C., Chi, P.-L., & Hsiao, L.-D. (2013). NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells. Toxicology and Applied Pharmacology, 272(2), 431–442.

    Article  CAS  PubMed  Google Scholar 

  82. Mann, D. L., & Spinale, F. G. (1998). Activation of matrix metalloproteinases in the failing human heart: Breaking the tie that binds. Circulation, 98(17), 1699–1702.

    Article  CAS  PubMed  Google Scholar 

  83. Kizaki, K., Ito, R., Okada, M., Yoshioka, K., Uchide, T., Temma, K., et al. (2006). Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice. Pharmacological Research., 53(4), 341–346.

    Article  CAS  PubMed  Google Scholar 

  84. Ivanová, M., Dovinová, I., Okruhlicová, Ľ, Tribulová, N., Šimončíková, P., Barte-ková, M., et al. (2012). Chronic cardiotoxicity of doxorubicin involves activation of myocardial and circulating matrix metalloproteinases in rats. Acta Pharmacologica Sinica., 33(4), 459–469. https://doi.org/10.1038/aps.2011.194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Slezak, J., Kura, B., Babal, P., Barancik, M., Ferko, M., Frimmel, K., et al. (2017). Potential markers and metabolic processes involved in the mechanism of radiation-induced heart injury. Canadian Journal of Physiology and Pharmacology., 95(10), 1190–1203.

    Article  CAS  PubMed  Google Scholar 

  86. Bai, P., Mabley, J. G., Liaudet, L., Virág, L., Szabó, C., & Pacher, P. (2004). Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity. Oncology Reports, 11(2), 505–508.

    CAS  PubMed  Google Scholar 

  87. O’Hanlon, R., Grasso, A., Roughton, M., Moon, J. C., Clark, S., Wage, R., et al. (2010). Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. Journal of the American College of Cardiology., 56(11), 867–874.

    Article  PubMed  Google Scholar 

  88. Liu, L. K., Ouyang, W., Zhao, X., Su, S. F., Yang, Y., Ding, W. J., et al. (2017). Pathogenesis and prevention of radiation-induced myocardial fibrosis. Asian Pacific Journal of Cancer Prevention: APJCP., 18(3), 583–587. https://doi.org/10.22034/APJCP.2017.18.3.583

    Article  PubMed  PubMed Central  Google Scholar 

  89. Nacif, M. S., Kawel, N., Lee, J. J., Chen, X., Yao, J., Zavodni, A., et al. (2012). Interstitial myocardial fibrosis assessed as extracellular volume fraction with low-radiation-dose cardiac CT. Radiology, 264(3), 876–883. https://doi.org/10.1148/radiol.12112458

    Article  PubMed  PubMed Central  Google Scholar 

  90. de Groot, C., Beukema, J. C., Langendijk, J. A., van der Laan, H. P., van Luijk, P., van Melle, J. P., et al. (2021). Radiation-induced myocardial fibrosis in long-term esophageal cancer survivors. International Journal of Radiation Oncology Biology Physics, 110(4), 1013–1021.

    Article  PubMed  Google Scholar 

  91. Farhad, H., Staziaki, P. V., Addison, D., Coelho-Filho, O. R., Shah, R. V., Mitchell, R. N., et al. (2016). Characterization of the changes in cardiac structure and function in mice treated with anthracyclines using serial cardiac magnetic resonance imaging. Circulation Cardiovascular Imaging., 9(12), e003584. https://doi.org/10.1161/CIRCIMAGING.115.003584

    Article  PubMed  PubMed Central  Google Scholar 

  92. Tandri, H., Saranathan, M., Rodriguez, E. R., Martinez, C., Bomma, C., Nasir, K., et al. (2005). Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging. Journal of the American College of Cardiology., 45(1), 98–103.

    Article  PubMed  Google Scholar 

  93. Iles, L., Pfluger, H., Phrommintikul, A., Cherayath, J., Aksit, P., Gupta, S. N., et al. (2008). Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. Journal of the American College of Cardiology., 52(19), 1574–1580. https://doi.org/10.1016/j.jacc.2008.06.049

    Article  PubMed  Google Scholar 

  94. Zhou, Z., Xu, L., Wang, R., Varga-Szemes, A., Durden, J. A., Joseph Schoepf, U., et al. (2019). Quantification of doxorubicin-induced interstitial myocardial fibrosis in a beagle model using equilibrium contrast-enhanced computed tomography: A comparative study with cardiac magnetic resonance T1-mapping. International Journal of Cardiology., 281, 150–155. https://doi.org/10.1016/j.ijcard.2019.01.021

    Article  PubMed  Google Scholar 

  95. Zhou, Z., Wang, R., Wang, H., Liu, Y., Lu, D., Sun, Z., et al. (2021). Myocardial extracellular volume fraction quantification in an animal model of the doxorubicin-induced myocardial fibrosis: A synthetic hematocrit method using 3T cardiac magnetic resonance. Quantitative Imaging in Medicine and Surgery., 11(2), 510–520. https://doi.org/10.21037/qims-20-501

    Article  PubMed  PubMed Central  Google Scholar 

  96. De Angelis, A., Urbanek, K., Cappetta, D., Piegari, E., Ciuffreda, L. P., Rivellino, A., et al. (2016). Doxorubicin cardiotoxicity and target cells: A broader perspective. Cardio-Oncology., 2(1), 1–8.

    Article  Google Scholar 

  97. Piegari, E., De Angelis, A., Cappetta, D., Russo, R., Esposito, G., Costantino, S., et al. (2013). Doxorubicin induces senescence and impairs function of human cardiac progenitor cells. Basic Research in Cardiology., 108(2), 1–18.

    Article  CAS  Google Scholar 

  98. Levick, S. P., Soto-Pantoja, D. R., Bi, J., Hundley, W. G., Widiapradja, A., Manteufel, E. J., et al. (2019). Doxorubicin-induced myocardial fibrosis involves the neurokinin-1 receptor and direct effects on cardiac fibroblasts. Heart, Lung & Circulation., 28(10), 1598–1605. https://doi.org/10.1016/j.hlc.2018.08.003

    Article  Google Scholar 

  99. Najafi, M., Motevaseli, E., Shirazi, A., Geraily, G., Rezaeyan, A., Norouzi, F., et al. (2018). Mechanisms of inflammatory responses to radiation and normal tissues toxicity: Clinical implications. International Journal of Radiation Biology, 94(4), 335–356. https://doi.org/10.1080/09553002.2018.1440092

    Article  CAS  PubMed  Google Scholar 

  100. Farhood, B., Hoseini-Ghahfarokhi, M., Motevaseli, E., Mirtavoos-Mahyari, H., Musa, A. E., & Najafi, M. (2020). TGF-β in radiotherapy: Mechanisms of tumor resistance and normal tissues injury. Pharmacological Research., 155, 104745.

    Article  CAS  PubMed  Google Scholar 

  101. Amini, P., Rezapoor, S., Shabeeb, D., Musa, A. E., Najafi, M., & Motevaseli, E. (2018). Evaluating the protective effect of a combination of curcumin and selenium-L-methionine on radiation induced dual oxidase upregulation. Pharmaceutical Sciences., 24(4), 340–345.

    Article  Google Scholar 

  102. Lin, F., Wang, N., & Zhang, T. C. (2012). The role of endothelial–mesenchymal transition in development and pathological process. IUBMB Life, 64(9), 717–723.

    Article  CAS  PubMed  Google Scholar 

  103. Song, S., Zhang, R., Cao, W., Fang, G., Yu, Y., Wan, Y., et al. (2019). Foxm1 is a critical driver of TGF-β-induced EndMT in endothelial cells through Smad2/3 and binds to the Snail promoter. Journal of Cellular Physiology., 234(6), 9052–9064.

    Article  CAS  PubMed  Google Scholar 

  104. Choi, K. J., Nam, J.-K., Kim, J.-H., Choi, S.-H., & Lee, Y.-J. (2020). Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage. Experimental & Molecular Medicine., 52(5), 781–792.

    Article  CAS  Google Scholar 

  105. Zhang, K., He, X., Zhou, Y., Gao, L., Qi, Z., Chen, J., et al. (2015). Atorvastatin ameliorates radiation-induced cardiac fibrosis in rats. Radiation Research, 184(6), 611–620. https://doi.org/10.1667/rr14075.1

    Article  CAS  PubMed  Google Scholar 

  106. Liu, H., Xiong, M., Xia, Y.-F., Cui, N.-J., Lu, R.-B., Deng, L., et al. (2009). Studies on pentoxifylline and tocopherol combination for radiation-induced heart disease in rats. International Journal of Radiation Oncology Biology Physics., 73(5), 1552–1559. https://doi.org/10.1016/j.ijrobp.2008.12.005

    Article  CAS  PubMed  Google Scholar 

  107. Tsai, T.-H., Lin, C.-J., Hang, C.-L., & Chen, W.-Y. (2019). Calcitriol attenuates doxorubicin-induced cardiac dysfunction and inhibits endothelial-to-mesenchymal transition in mice. Cells, 8(8), 865.

    Article  CAS  PubMed Central  Google Scholar 

  108. Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J., et al. (2021). Hydrogen sulfide ameliorates doxorubicin-induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway. Molecular Medicine Reports, 23(4), 1–11.

    Article  CAS  Google Scholar 

  109. Luo, L.-F., Guan, P., Qin, L.-Y., Wang, J.-X., Wang, N., & Ji, E.-S. (2021). Astragaloside IV inhibits adriamycin-induced cardiac ferroptosis by enhancing Nrf2 signaling. Molecular and Cellular Biochemistry, 476(7), 2603–2611. https://doi.org/10.1007/s11010-021-04112-6

    Article  CAS  PubMed  Google Scholar 

  110. Arafa, M. H., Mohammad, N. S., Atteia, H. H., & Abd-Elaziz, H. R. (2014). Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats. Journal of Physiology and Biochemistry, 70(3), 701–711.

    Article  CAS  PubMed  Google Scholar 

  111. Saleh, M. A., Antar, S. A., Hazem, R. M., & El-Azab, M. F. (2020). Pirfenidone and vitamin D ameliorate cardiac fibrosis induced by doxorubicin in ehrlich ascites carcinoma bearing mice: Modulation of monocyte chemoattractant protein-1 and Jun N-terminal kinase-1 pathways. Pharmaceuticals, 13(11), 348.

    Article  CAS  PubMed Central  Google Scholar 

  112. Sahna, E., Parlakpinar, H., Ozer, M. K., Ozturk, F., Ozugurlu, F., & Acet, A. (2003). Melatonin protects against myocardial doxorubicin toxicity in rats: Role of physiological concentrations. Journal of Pineal Research, 35(4), 257–261.

    Article  CAS  PubMed  Google Scholar 

  113. Shaty, M. H., Arif, I. S., Al-Ezzi, M. I., & Hanna, D. B. (2018). Metformin attenuate fibrosis in both acute and chronic doxorubicin cardiotoxicity in rabbits. Journal of Pharmaceutical Sciences and Research, 10(6), 1559–1565.

    CAS  Google Scholar 

  114. Katamura, M., Iwai-Kanai, E., Nakaoka, M., Okawa, Y., Ariyoshi, M., Mita, Y., et al. (2014). Curcumin attenuates doxorubicin-induced cardiotoxicity by inducing autophagy via the regulation of JNK phosphorylation. Journal of Clinical and Experimental Cardiology, 5(09), 1–8.

    Article  Google Scholar 

  115. van der Veen, S. J., Ghobadi, G., de Boer, R. A., Faber, H., Cannon, M. V., Nagle, P. W., et al. (2015). ACE inhibition attenuates radiation-induced cardiopulmonary damage. Radiotherapy and Oncology, 114(1), 96–103. https://doi.org/10.1016/j.radonc.2014.11.017

    Article  CAS  PubMed  Google Scholar 

  116. Vatanen, A., Sarkola, T., Ojala, T. H., Turanlahti, M., Jahnukainen, T., Saarinen-Pihkala, U. M., et al. (2015). Radiotherapy-related arterial intima thickening and plaque formation in childhood cancer survivors detected with very-high resolution ultrasound during young adulthood. Pediatric Blood & Cancer, 62(11), 2000–2006.

    Article  CAS  Google Scholar 

  117. Huang, T. L., Hsu, H. C., Chen, H. C., Lin, H. C., Chien, C. Y., Fang, F. M., et al. (2013). Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma. Radiation Oncology., 8(1), 1–6.

    Article  CAS  Google Scholar 

  118. Schultz-Hector, S., & Trott, K. R. (2007). Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data? International Journal of Radiation Oncology Biology Physics, 67(1), 10–18. https://doi.org/10.1016/j.ijrobp.2006.08.071

    Article  CAS  PubMed  Google Scholar 

  119. Berliner, S., Rahima, M., Sidi, Y., Teplitsky, Y., Zohar, Y., Nussbaum, B., et al. (1990). Acute coronary events following cisplatin-based chemotherapy. Cancer Investigation, 8(6), 583–586.

    Article  CAS  PubMed  Google Scholar 

  120. Eckman, D. M., Stacey, R. B., Rowe, R., Dagostino, R., Jr., Kock, N. D., Sane, D. C., et al. (2013). Weekly doxorubicin increases coronary arteriolar wall and adventitial thickness. PLoS ONE, 8(2), e57554. https://doi.org/10.1371/journal.pone.0057554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Vogelzang, N. J., Frenning, D. H., & Kennedy, B. J. (1980). Coronary artery disease after treatment with bleomycin and vinblastine. Cancer Treatment Reports, 64(10–11), 1159–1160.

    CAS  PubMed  Google Scholar 

  122. Stewart, F. A. (2012). Mechanisms and dose-response relationships for radiation-induced cardiovascular disease. Annals of the ICRP, 41(3–4), 72–79. https://doi.org/10.1016/j.icrp.2012.06.031

    Article  CAS  PubMed  Google Scholar 

  123. Khaled, S., Gupta, K. B., & Kucik, D. F. (2012). Ionizing radiation increases adhesiveness of human aortic endothelial cells via a chemokine-dependent mechanism. Radiation Research, 177(5), 594–601. https://doi.org/10.1667/rr2557.1

    Article  CAS  PubMed  Google Scholar 

  124. Haubner, F., Ohmann, E., Pohl, F., Prantl, L., Strutz, J., & Gassner, H. G. (2013). Effects of radiation on the expression of adhesion molecules and cytokines in a static model of human dermal microvascular endothelial cells. Clinical Hemorheology and Microcirculation, 54(4), 371–379. https://doi.org/10.3233/ch-2012-1626

    Article  CAS  PubMed  Google Scholar 

  125. Cuomo, J. R., Javaheri, S. P., Sharma, G. K., Kapoor, D., Berman, A. E., & Weintraub, N. L. (2018). How to prevent and manage radiation-induced coronary artery disease. Heart, 104(20), 1647–1653. https://doi.org/10.1136/heartjnl-2017-312123

    Article  PubMed  Google Scholar 

  126. Hoving, S., Heeneman, S., Gijbels, M. J., te Poele, J. A., Russell, N. S., Daemen, M. J., et al. (2008). Single-dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE(-/-) mice. International Journal of Radiation Oncology Biology Physics, 71(3), 848–857. https://doi.org/10.1016/j.ijrobp.2008.02.031

    Article  CAS  PubMed  Google Scholar 

  127. Basavaraju, S. R., & Easterly, C. E. (2002). Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. Medical Physics, 29(10), 2391–2403. https://doi.org/10.1118/1.1509442

    Article  PubMed  Google Scholar 

  128. He, F., & Zuo, L. (2015). Redox roles of reactive oxygen species in cardiovascular diseases. International Journal of Molecular Sciences, 16(11), 27770–27780. https://doi.org/10.3390/ijms161126059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Pfenniger, A., Chanson, M., & Kwak, B. R. (2013). Connexins in atherosclerosis. Biochimica et Biophysica Acta, 1828(1), 157–166. https://doi.org/10.1016/j.bbamem.2012.05.011

    Article  CAS  PubMed  Google Scholar 

  130. Ohshima, Y., Tsukimoto, M., Harada, H., & Kojima, S. (2012). Involvement of connexin43 hemichannel in ATP release after γ-irradiation. Journal of Radiation Research, 53(4), 551–557. https://doi.org/10.1093/jrr/rrs014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Carta, S., Castellani, P., Delfino, L., Tassi, S., Vene, R., & Rubartelli, A. (2009). DAMPs and inflammatory processes: The role of redox in the different outcomes. Journal of Leukocyte Biology, 86(3), 549–555.

    Article  CAS  PubMed  Google Scholar 

  132. Ramadan, R., Baatout, S., Aerts, A., & Leybaert, L. (2021). The role of connexin proteins and their channels in radiation-induced atherosclerosis. Cellular and Molecular Life Sciences., 78(7), 3087–3103. https://doi.org/10.1007/s00018-020-03716-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Ramadan, R., Vromans, E., Anang, D. C., Goetschalckx, I., Hoorelbeke, D., Decrock, E., et al. (2020). Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage. Frontiers in Pharmacology., 11, e00212. https://doi.org/10.3389/fphar.2020.00212

    Article  CAS  Google Scholar 

  134. Viczenczova, C., Kura, B., Egan Benova, T., Yin, C., Kukreja, R. C., Slezak, J., et al. (2018). Irradiation-induced cardiac connexin-43 and miR-21 responses are hampered by treatment with atorvastatin and aspirin. International Journal of Molecular Sciences, 19(4), 1128. https://doi.org/10.3390/ijms19041128

    Article  CAS  PubMed Central  Google Scholar 

  135. Sato, A., Yoshihisa, A., Miyata-Tatsumi, M., Oikawa, M., Kobayashi, A., Ishida, T., et al. (2019). Valvular heart disease as a possible predictor of trastuzumab-induced cardiotoxicity in patients with breast cancer. Molecular and Clinical Oncology, 10(1), 37–42.

    CAS  PubMed  Google Scholar 

  136. Cella, L., Oh, J. H., Deasy, J. O., Palma, G., Liuzzi, R., D’avino, V., et al. (2015). Predicting radiation-induced valvular heart damage. Acta Oncologica., 54(10), 1796–1804.

    Article  CAS  PubMed  Google Scholar 

  137. Bijl, J. M., Roos, M. M., van Leeuwen-Segarceanu, E. M., Vos, J. M., Bos, W.-J.W., Biesma, D. H., et al. (2016). Assessment of valvular disorders in survivors of Hodgkin’s lymphoma treated by mediastinal radiotherapy±chemotherapy. The American Journal of Cardiology., 117(4), 691–696.

    Article  PubMed  Google Scholar 

  138. Gujral, D. M., Lloyd, G., & Bhattacharyya, S. (2016). Radiation-induced valvular heart disease. Heart, 102(4), 269–276.

    Article  CAS  PubMed  Google Scholar 

  139. Nadlonek, N. A., Weyant, M. J., Jessica, A. Y., Cleveland, J. C., Jr., Reece, T. B., Meng, X., et al. (2012). Radiation induces osteogenesis in human aortic valve interstitial cells. The Journal of Thoracic and Cardiovascular Surgery., 144(6), 1466–1470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Wang, H., Wei, J., Zheng, Q., Meng, L., Xin, Y., Yin, X., et al. (2019). Radiation-induced heart disease: A review of classification, mechanism and prevention. International Journal of Biological Sciences, 15(10), 2128–2138. https://doi.org/10.7150/ijbs.35460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Barrick, C. J., Roberts, R. B., Rojas, M., Rajamannan, N. M., Suitt, C. B., O’Brien, K. D., et al. (2009). Reduced EGFR causes abnormal valvular differentiation leading to calcific aortic stenosis and left ventricular hypertrophy in C57BL/6J but not 129S1/SvImJ mice. American Journal of Physiology-Heart and Circulatory Physiology., 297(1), H65–H75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Gorini, S., De Angelis, A., Berrino, L., Malara, N., Rosano, G., & Ferraro, E. (2018). Chemotherapeutic drugs and mitochondrial dysfunction: Focus on doxorubicin, trastuzumab, and sunitinib. Oxidative Medicine and Cellular Longevity, 2018, 7582730. https://doi.org/10.1155/2018/7582730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Grazette, L. P., Boecker, W., Matsui, T., Semigran, M., Force, T. L., Hajjar, R. J., et al. (2004). Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes: Implications for herceptin-induced cardiomyopathy. Journal of the American College of Cardiology., 44(11), 2231–2238. https://doi.org/10.1016/j.jacc.2004.08.066

    Article  CAS  PubMed  Google Scholar 

  144. Sun, L., Wang, H., Yu, S., Zhang, L., Jiang, J., & Zhou, Q. (2022). Herceptin induces ferroptosis and mitochondrial dysfunction in H9c2 cells. International Journal of Molecular Medicine, 49(2), 17. https://doi.org/10.3892/ijmm.2021.5072

    Article  CAS  PubMed  Google Scholar 

  145. Karabay, C. Y., Kocabay, G., Kalayci, A., Zehir, R., & Tanboga, H. (2010). Mitral regurgitation due to papillary muscle dyssynchrony during trastuzumab treatment. Cardiology, 117(4), 296–300. https://doi.org/10.1159/000323834

    Article  PubMed  Google Scholar 

  146. Fortuni, F., Bax, J. J., & Delgado, V. (2021). Changing the paradigm in the management of valvular heart disease. Circulation, 143(3), 209–211. https://doi.org/10.1161/CIRCULATIONAHA.120.050763

    Article  PubMed  Google Scholar 

  147. Grela-Wojewoda, A., Niemiec, J., Sas-Korczyńska, B., Zemełka, T., Puskulluoglu, M., & Wysocki, W. M. et al. (2022). Adjuvant combined therapy with trastuzumab in patients with HER2-positive breast cancer and cardiac alterations: Implications for optimal cardio-oncology care. Polish Archives of Internal Medicine.

  148. Ewer, S. M., & Ewer, M. S. (2008). Cardiotoxicity profile of trastuzumab. Drug Safety, 31(6), 459–467.

    Article  CAS  PubMed  Google Scholar 

  149. Guarneri, V., Lenihan, D. J., Valero, V., Durand, J. B., Broglio, K., Hess, K. R., et al. (2006). Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience. Journal of Clinical Oncology, 24(25), 4107–15. https://doi.org/10.1200/jco.2005.04.9551

    Article  CAS  PubMed  Google Scholar 

  150. Saiki, H., Moulay, G., Guenzel, A. J., Liu, W., Decklever, T. D., Classic, K. L., et al. (2017). Experimental cardiac radiation exposure induces ventricular diastolic dysfunction with preserved ejection fraction. American Journal of Physiology-Heart and Circulatory Physiology., 313(2), H392–H407.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Dobaczewski, M., Chen, W., & Frangogiannis, N. G. (2011). Transforming growth factor (TGF)-β signaling in cardiac remodeling. Journal of Molecular and Cellular Cardiology, 51(4), 600–606. https://doi.org/10.1016/j.yjmcc.2010.10.033

    Article  CAS  PubMed  Google Scholar 

  152. Monceau, V., Meziani, L., Strup-Perrot, C., Morel, E., Schmidt, M., Haagen, J., et al. (2013). Enhanced sensitivity to low dose irradiation of ApoE-/- mice mediated by early pro-inflammatory profile and delayed activation of the TGFβ1 cascade involved in fibrogenesis. PLoS ONE, 8(2), e57052. https://doi.org/10.1371/journal.pone.0057052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Luk, A., Ahn, E., Soor, G. S., & Butany, J. (2009). Dilated cardiomyopathy: A review. Journal of Clinical Pathology., 62(3), 219–225.

    Article  CAS  PubMed  Google Scholar 

  154. Cuomo, J. R., Sharma, G. K., Conger, P. D., & Weintraub, N. L. (2016). Novel concepts in radiation-induced cardiovascular disease. World Journal of Cardiology, 8(9), 504–519. https://doi.org/10.4330/wjc.v8.i9.504

    Article  PubMed  PubMed Central  Google Scholar 

  155. Harvey, P. A., & Leinwand, L. A. (2011). The cell biology of disease: Cellular mechanisms of cardiomyopathy. The Journal of Cell Biology., 194(3), 355–365. https://doi.org/10.1083/jcb.201101100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Maisel, W. H., & Stevenson, L. W. (2003). Atrial fibrillation in heart failure: Epidemiology, pathophysiology, and rationale for therapy. The American Journal of Cardiology., 91(6), 2–8.

    Article  Google Scholar 

  157. Stevenson, W. G., & Stevenson, L. W. (1999). Atrial fibrillation in heart failure (pp. 910–911). Waltham: Mass Medical Soc.

    Google Scholar 

  158. O’Neal, W. T., Lakoski, S. G., Qureshi, W., Judd, S. E., Howard, G., Howard, V. J., et al. (2015). Relation between cancer and atrial fibrillation (from the REasons for Geographic And Racial Differences in Stroke Study). The American Journal of Cardiology., 115(8), 1090–1094.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Yang, X., Li, X., Yuan, M., Tian, C., Yang, Y., Wang, X., et al. (2018). Anticancer therapy-induced atrial fibrillation: Electrophysiology and related mechanisms. Frontiers in Pharmacology., 9, 1058. https://doi.org/10.3389/fphar.2018.01058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Grandi, E., & Herren, A. (2014). CaMKII-dependent regulation of cardiac Na+ homeostasis. Frontiers in Pharmacology., 5, 41. https://doi.org/10.3389/fphar.2014.00041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Strigli, A., Raab, C., Hessler, S., Huth, T., Schuldt, A. J. T., Alzheimer, C., et al. (2018). Doxorubicin induces caspase-mediated proteolysis of KV7.1. Communications Biology, 1(1), 155. https://doi.org/10.1038/s42003-018-0162-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Swaminathan, P. D., Purohit, A., Hund, T. J., & Anderson, M. E. (2012). Calmodulin-dependent protein kinase II: Linking heart failure and arrhythmias. Circulation Research., 110(12), 1661–1677. https://doi.org/10.1161/CIRCRESAHA.111.243956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Greer-Short, A., Musa, H., Alsina, K. M., Ni, L., Word, T. A., Reynolds, J. O., et al. (2020). Calmodulin kinase II regulates atrial myocyte late sodium current, calcium handling, and atrial arrhythmia. Heart Rhythm, 17(3), 503–511. https://doi.org/10.1016/j.hrthm.2019.10.016

    Article  PubMed  Google Scholar 

  164. Benjanuwattra, J., Siri-Angkul, N., Chattipakorn, S. C., & Chattipakorn, N. (2020). Doxorubicin and its proarrhythmic effects: A comprehensive review of the evidence from experimental and clinical studies. Pharmacological Research., 151, 104542.

    Article  CAS  PubMed  Google Scholar 

  165. McMullen, J. R., Boey, E. J. H., Ooi, J. Y. Y., Seymour, J. F., Keating, M. J., & Tam, C. S. (2014). Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling. Blood, 124(25), 3829–3830. https://doi.org/10.1182/blood-2014-10-604272

    Article  CAS  PubMed  Google Scholar 

  166. Zhao, L. (2019). Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. Anatolian Journal of Cardiology., 22(5), 232.

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Darling, H. (2015). Cisplatin induced bradycardia. International Journal of Cardiology., 182, 304–306.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Not Applicable.

Author information

Authors and Affiliations

Authors

Contributions

All authors were involved in the preparing the first draft. All authors also approved the final format of the article.

Corresponding author

Correspondence to Tan Panpan.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Research Involving Human and Animal Rights

This article does not contain human or animal studies performed by any of the authors.

Informed Consent

Not Applicable.

Additional information

Handling Editor: Atsushi Sugiyama.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Panpan, T., Yuchen, D., Xianyong, S. et al. Cardiac Remodelling Following Cancer Therapy: A Review. Cardiovasc Toxicol 22, 771–786 (2022). https://doi.org/10.1007/s12012-022-09762-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-022-09762-6

Keywords

Navigation