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Intermittent Hypoxic Preconditioning Plays a Cardioprotective Role in Doxorubicin-Induced Cardiomyopathy

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Abstract

Intermittent hypoxic preconditioning (IHP) is a well-established cardioprotective intervention in models of ischemia/reperfusion injury. Nevertheless, the significance of IHP in different cardiac pathologies remains elusive. In order to investigate the role of IHP and its effects on calcium-dependent signalization in HF, we employed a model of cardiomyopathy induced by doxorubicin (Dox), a widely used drug from the class of cardiotoxic antineoplastics, which was i.p. injected to Wistar rats (4 applications of 4 mg/kg/week). IHP-treated group was exposed to IHP for 2 weeks prior to Dox administration. IHP ameliorated Dox-induced reduction in cardiac output. Western blot analysis revealed increased expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) while the expression of hypoxia inducible factor (HIF)-1-α, which is a crucial regulator of hypoxia-inducible genes, was not changed. Animals administered with Dox had further decreased expression of TRPV1 and TRPV4 (transient receptor potential, vanilloid subtype) ion channels along with suppressed Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation. In summary, IHP-mediated improvement in cardiac output in the model of Dox-induced cardiomyopathy is likely a result of increased SERCA2a expression which could implicate IHP as a potential protective intervention in Dox cardiomyopathy, however, further analysis of observed effects is still required.

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References

  1. Chung, W. B., & Youn, H. J. (2016). Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity. The Korean Journal of Internal Medicine, 31(4), 625–633. https://doi.org/10.3904/kjim.2016.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Volkova, M., & Russell, R., 3rd. (2011). Anthracycline cardiotoxicity: Prevalence, pathogenesis and treatment. Current Cardiology Reviews, 7(4), 214–220. https://doi.org/10.2174/157340311799960645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rivera, E. (2003). Liposomal anthracyclines in metastatic breast cancer: Clinical update. The oncologist, 8(Suppl 2), 3–9. https://doi.org/10.1634/theoncologist.8-suppl_2-3

    Article  CAS  PubMed  Google Scholar 

  4. Martins-Teixeira, M. B., & Carvalho, I. (2020). Antitumour anthracyclines: progress and perspectives. ChemMedChem, 15(11), 933–948. https://doi.org/10.1002/cmdc.202000131

    Article  CAS  PubMed  Google Scholar 

  5. Shevchuk, O. O., Posokhova, E. A., Sakhno, L. A., & Nikolaev, V. G. (2012). Theoretical ground for adsorptive therapy of anthracyclines cardiotoxicity. Experimental Oncology, 34(4), 314–322.

    CAS  PubMed  Google Scholar 

  6. Nebigil, C. G., & Désaubry, L. (2018). Updates in anthracycline-mediated cardiotoxicity. Frontiers in Pharmacology, 9, 1262. https://doi.org/10.3389/fphar.2018.01262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sag, C. M., Köhler, A. C., Anderson, M. E., Backs, J., & Maier, L. S. (2011). CaMKII-dependent SR Ca leak contributes to doxorubicin-induced impaired Ca handling in isolated cardiac myocytes. Journal of Molecular and Cellular Cardiology, 51(5), 749–759. https://doi.org/10.1016/j.yjmcc.2011.07.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Llach, A., Mazevet, M., Mateo, P., Villejouvert, O., Ridoux, A., Rucker-Martin, C., Ribeiro, M., Fischmeister, R., Crozatier, B., Benitah, J. P., Morel, E., & Gómez, A. M. (2019). Progression of excitation-contraction coupling defects in doxorubicin cardiotoxicity. Journal of Molecular and Cellular Cardiology, 126, 129–139. https://doi.org/10.1016/j.yjmcc.2018.11.019

    Article  CAS  PubMed  Google Scholar 

  9. Pecoraro, M., Rodríguez-Sinovas, A., Marzocco, S., Ciccarelli, M., Iaccarino, G., Pinto, A., & Popolo, A. (2017). Cardiotoxic effects of short-term doxorubicin administration: involvement of connexin 43 in calcium impairment. International Journal of Molecular Sciences, 18(10), 2121. https://doi.org/10.3390/ijms18102121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fernandez-Chas, M., Curtis, M. J., & Niederer, S. A. (2018). Mechanism of doxorubicin cardiotoxicity evaluated by integrating multiple molecular effects into a biophysical model. British Journal of Pharmacology, 175(5), 763–781. https://doi.org/10.1111/bph.14104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhu, W., Reuter, S., & Field, L. J. (2019). Targeted expression of cyclin D2 ameliorates late stage anthracycline cardiotoxicity. Cardiovascular Research, 115(5), 960–965. https://doi.org/10.1093/cvr/cvy273

    Article  CAS  PubMed  Google Scholar 

  12. Kraft, J., Grille, W., Appelt, M., Hossfeld, D. K., Eichelbaum, M., Koslowski, B., Quabeck, K., Kuse, R., Büchner, T., & Hiddemann, W. (1990). Effects of verapamil on anthracycline-induced cardiomyopathy: Preliminary results of a prospective multicenter trial. Haematology and Blood Transfusion, 33, 566–570. https://doi.org/10.1007/978-3-642-74643-7_103

    Article  CAS  PubMed  Google Scholar 

  13. Milei, J., Marantz, A., Alé, J., Vazquez, A., & Buceta, J. E. (1987). Prevention of adriamycin-induced cardiotoxicity by prenylamine: A pilot double blind study. Cancer Drug Delivery, 4(2), 129–136. https://doi.org/10.1089/cdd.1987.4.129

    Article  CAS  PubMed  Google Scholar 

  14. Lu, M. J., Chen, Y. S., Huang, H. S., & Ma, M. C. (2014). Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase/transient receptor potential vanilloid 1 pathway. Basic Research in Cardiology, 109(4), 414. https://doi.org/10.1007/s00395-014-0414-0

    Article  CAS  PubMed  Google Scholar 

  15. Hu, K., Deng, W., Yang, J., Wei, Y., Wen, C., Li, X., Chen, Q., Ke, D., & Li, G. (2020). Intermittent hypoxia reduces infarct size in rats with acute myocardial infarction: A systematic review and meta-analysis. BMC Cardiovascular Disorders, 20(1), 422. https://doi.org/10.1186/s12872-020-01702-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jarrard, C. P., Nagel, M. J., Stray-Gundersen, S., Tanaka, H., & Lalande, S. (2021). Hypoxic preconditioning attenuates ischemia-reperfusion injury in young healthy adults. Journal of Applied Physiology (Bethesda, Md: 1985), 130(3), 846–852. https://doi.org/10.1152/japplphysiol.00772.2020

    Article  PubMed  Google Scholar 

  17. Baumgarten, K. M., Gerstenblith, G., & Weiss, R. G. (1999). High extracellular K+ during hypoxic preconditioning episodes attenuates the post-ischemic contractile and ionic benefits of preconditioning. Journal of Molecular and Cellular Cardiology, 31(1), 203–213. https://doi.org/10.1006/jmcc.1998.0860

    Article  CAS  PubMed  Google Scholar 

  18. Liu, X., Xu, F., Fu, Y., Liu, F., Sun, S., & Wu, X. (2006). Calreticulin induces delayed cardioprotection through mitogen-activated protein kinases. Proteomics, 6(13), 3792–3800. https://doi.org/10.1002/pmic.200500906

    Article  CAS  PubMed  Google Scholar 

  19. Wu, X., Liu, X., Zhu, X., & Tang, C. (2007). Hypoxic preconditioning induces delayed cardioprotection through p38 MAPK-mediated calreticulin upregulation. Shock (Augusta, Ga), 27(5), 572–577. https://doi.org/10.1097/01.shk.0000246901.58068.a8

    Article  CAS  PubMed  Google Scholar 

  20. Cai, Z., Manalo, D. J., Wei, G., Rodriguez, E. R., Fox-Talbot, K., Lu, H., Zweier, J. L., & Semenza, G. L. (2003). Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation, 108(1), 79–85. https://doi.org/10.1161/01.CIR.0000078635.89229.8A

    Article  CAS  PubMed  Google Scholar 

  21. Tanaka, T., Yamaguchi, J., Shoji, K., & Nangaku, M. (2012). Anthracycline inhibits recruitment of hypoxia-inducible transcription factors and suppresses tumor cell migration and cardiac angiogenic response in the host. The Journal of Biological Chemistry, 287(42), 34866–34882. https://doi.org/10.1074/jbc.M112.374587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Graziani, S., Scorrano, L., & Pontarin, G. (2022). Transient exposure of endothelial cells to doxorubicin leads to long-lasting vascular endothelial growth factor receptor 2 downregulation. Cells, 11(2), 210. https://doi.org/10.3390/cells11020210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chiusa, M., Hool, S. L., Truetsch, P., Djafarzadeh, S., Jakob, S. M., Seifriz, F., Scherer, S. J., Suter, T. M., Zup**er, C., & Zbinden, S. (2012). Cancer therapy modulates VEGF signaling and viability in adult rat cardiac microvascular endothelial cells and cardiomyocytes. Journal of Molecular and Cellular Cardiology, 52(5), 1164–1175. https://doi.org/10.1016/j.yjmcc.2012.01.022

    Article  CAS  PubMed  Google Scholar 

  24. Huang, Y., Hickey, R. P., Yeh, J. L., Liu, D., Dadak, A., Young, L. H., Johnson, R. S., & Giordano, F. J. (2004). Cardiac myocyte-specific HIF-1alpha deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 18(10), 1138–1140. https://doi.org/10.1096/fj.04-1510fje

    Article  CAS  PubMed  Google Scholar 

  25. Silter, M., Kögler, H., Zieseniss, A., Wilting, J., Schäfer, K., Toischer, K., Rokita, A. G., Breves, G., Maier, L. S., & Katschinski, D. M. (2010). Impaired Ca(2+)-handling in HIF-1alpha(+/-) mice as a consequence of pressure overload. Pflugers Archiv : European Journal of Physiology, 459(4), 569–577. https://doi.org/10.1007/s00424-009-0748-x

    Article  CAS  PubMed  Google Scholar 

  26. Rath, G., Saliez, J., Behets, G., Romero-Perez, M., Leon-Gomez, E., Bouzin, C., Vriens, J., Nilius, B., Feron, O., & Dessy, C. (2012). Vascular hypoxic preconditioning relies on TRPV4-dependent calcium influx and proper intercellular gap junctions communication. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(9), 2241–2249. https://doi.org/10.1161/ATVBAHA.112.252783

    Article  CAS  PubMed  Google Scholar 

  27. Hof, T., Chaigne, S., Récalde, A., Sallé, L., Brette, F., & Guinamard, R. (2019). Transient receptor potential channels in cardiac health and disease. Nature Reviews. Cardiology, 16(6), 344–360. https://doi.org/10.1038/s41569-018-0145-2

    Article  PubMed  Google Scholar 

  28. Kang, Y., Wang, W., Zhao, H., Qiao, Z., Shen, X., & He, B. (2017). Assessment of Subclinical Doxorubicin-induced Cardiotoxicity in a Rat Model by Speckle-Tracking Imaging. Arquivos brasileiros de cardiologia. https://doi.org/10.5935/abc.20170097

    Article  PubMed  PubMed Central  Google Scholar 

  29. **, L., Tekin, D., Gursoy, E., Salloum, F., Levasseur, J. E., & Kukreja, R. C. (2002). Evidence that NOS2 acts as a trigger and mediator of late preconditioning induced by acute systemic hypoxia. American Journal of Physiology. Heart and Circulatory Physiology, 283(1), 5–12. https://doi.org/10.1152/ajpheart.00920.2001

    Article  Google Scholar 

  30. Szobi, A., Gonçalvesová, E., Varga, Z. V., Leszek, P., Kuśmierczyk, M., Hulman, M., Kyselovič, J., Ferdinandy, P., & Adameová, A. (2017). Analysis of necroptotic proteins in failing human hearts. Journal of Translational Medicine, 15(1), 86. https://doi.org/10.1186/s12967-017-1189-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Moritz, C. P. (2017). Tubulin or not tubulin: heading toward total protein staining as loading control in western blots. Proteomics. https://doi.org/10.1002/pmic.201600189

    Article  PubMed  Google Scholar 

  32. Curtis, M. J., Alexander, S., Cirino, G., Docherty, J. R., George, C. H., Giembycz, M. A., Hoyer, D., Insel, P. A., Izzo, A. A., Ji, Y., MacEwan, D. J., Sobey, C. G., Stanford, S. C., Teixeira, M. M., Wonnacott, S., & Ahluwalia, A. (2018). Experimental design and analysis and their reporting II: Updated and simplified guidance for authors and peer reviewers. British Journal of Pharmacology, 175(7), 987–993. https://doi.org/10.1111/bph.14153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Rathod, N., Bak, J. J., Primeau, J. O., Fisher, M. E., Espinoza-Fonseca, L. M., Lemieux, M. J., & Young, H. S. (2021). Nothing regular about the regulins: distinct functional properties of SERCA transmembrane peptide regulatory subunits. International Journal of Molecular Sciences, 22(16), 8891. https://doi.org/10.3390/ijms22168891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chang, H. H., Hsu, S. P., & Chien, C. T. (2019). Intrarenal transplantation of hypoxic preconditioned mesenchymal stem cells improves glomerulonephritis through anti-oxidation, anti-ER stress, anti-inflammation, anti-apoptosis, and anti-autophagy. Antioxidants (Basel, Switzerland), 9(1), 2. https://doi.org/10.3390/antiox9010002

    Article  CAS  PubMed  Google Scholar 

  35. Chang, J. C., Lien, C. F., Lee, W. S., Chang, H. R., Hsu, Y. C., Luo, Y. P., Jeng, J. R., Hsieh, J. C., & Yang, K. T. (2019). Intermittent hypoxia prevents myocardial mitochondrial Ca2+ overload and cell death during ischemia/reperfusion: The role of reactive oxygen species. Cells, 8(6), 564. https://doi.org/10.3390/cells8060564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhong, N., Zhang, Y., Zhu, H. F., & Zhou, Z. N. (2000). Intermittent hypoxia exposure prevents mtDNA deletion and mitochondrial structure damage produced by ischemia/reperfusion injury. Sheng li xue bao: Acta physiologica Sinica, 52(5), 375–380.

    CAS  PubMed  Google Scholar 

  37. Wang, Z., & Si, L. Y. (2013). Hypoxia-inducible factor-1α and vascular endothelial growth factor in the cardioprotective effects of intermittent hypoxia in rats. Upsala Journal of Medical Sciences, 118(2), 65–74. https://doi.org/10.3109/03009734.2013.766914

    Article  PubMed  PubMed Central  Google Scholar 

  38. Semenza, G. L. (2014). Hypoxia-inducible factor 1 and cardiovascular disease. Annual Review of Physiology, 76, 39–56. https://doi.org/10.1146/annurev-physiol-021113-170322

    Article  CAS  PubMed  Google Scholar 

  39. Li, J., Li, C., Yuan, W., Wu, J., Li, J., Li, Z., & Zhao, Y. (2021). Targeted temperature management suppresses hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a pig model of cardiac arrest. Neurocritical caRe, 35(2), 379–388. https://doi.org/10.1007/s12028-020-01166-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. **e, H. C., Li, J. G., & He, J. P. (2017). Differential responsiveness in VEGF receptor subtypes to hypoxic stress in various tissues of plateau animals. Physiological Research, 66(2), 357–362. https://doi.org/10.33549/physiolres.933408

    Article  CAS  PubMed  Google Scholar 

  41. Lin, J. S., Chen, Y. S., Chiang, H. S., & Ma, M. C. (2008). Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury: Role of erythropoietin on progenitor cell mobilization. The Journal of Physiology, 586(23), 5757–5769. https://doi.org/10.1113/jphysiol.2008.160887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Simůnek, T., Sterba, M., Holecková, M., Kaplanová, J., Klimtová, I., Adamcová, M., Gersl, V., & Hrdina, R. (2005). Myocardial content of selected elements in experimental anthracycline-induced cardiomyopathy in rabbits. Biometals : An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 18(2), 163–169. https://doi.org/10.1007/s10534-004-4491-7

    Article  CAS  PubMed  Google Scholar 

  43. Babick, A. P., Cantor, E. J., Babick, J. T., Takeda, N., Dhalla, N. S., & Netticadan, T. (2004). Cardiac contractile dysfunction in J2N-k cardiomyopathic hamsters is associated with impaired SR function and regulation. American Journal of Physiology. Cell Physiology, 287(5), C1202–C1208. https://doi.org/10.1152/ajpcell.00155.2004

    Article  CAS  PubMed  Google Scholar 

  44. Ji, Y., Lalli, M. J., Babu, G. J., Xu, Y., Kirkpatrick, D. L., Liu, L. H., Chiamvimonvat, N., Walsh, R. A., Shull, G. E., & Periasamy, M. (2000). Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function. The Journal of Biological Chemistry, 275(48), 38073–38080. https://doi.org/10.1074/jbc.M004804200

    Article  CAS  PubMed  Google Scholar 

  45. Ezzitouny, M., Roselló-Lletí, E., Portolés, M., Sánchez-Lázaro, I., Arnau-Vives, M. Á., Tarazón, E., Gil-Cayuela, C., Lozano-Edo, S., López-Vilella, R., Almenar-Bonet, L., & Martínez-Dolz, L. (2021). Value of SERCA2a as a biomarker for the identification of patients with heart failure requiring circulatory support. Journal of Personalized Medicine, 11(11), 1122. https://doi.org/10.3390/jpm11111122

    Article  PubMed  PubMed Central  Google Scholar 

  46. Samuel, T. J., Rosenberry, R. P., Lee, S., & Pan, Z. (2018). Correcting calcium dysregulation in chronic heart failure using SERCA2a gene therapy. International Journal of Molecular Sciences, 19(4), 1086. https://doi.org/10.3390/ijms19041086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lenčová-Popelová, O., Jirkovský, E., Mazurová, Y., Lenčo, J., Adamcová, M., Šimůnek, T., Geršl, V., & Štěrba, M. (2014). Molecular remodeling of left and right ventricular myocardium in chronic anthracycline cardiotoxicity and post-treatment follow up. PLoS One, 9(5), e96055. https://doi.org/10.1371/journal.pone.0096055

    Article  PubMed  PubMed Central  Google Scholar 

  48. Matsuda, N., Morgan, K. G., & Sellke, F. W. (1999). Preconditioning improves cardioplegia-related coronary microvascular smooth muscle hypercontractility: Role of KATP channels. The Journal of Thoracic and Cardiovascular Surgery, 118(3), 438–445. https://doi.org/10.1016/S0022-5223(99)70180-7

    Article  CAS  PubMed  Google Scholar 

  49. Westberg, J. A., Serlachius, M., Lankila, P., & Andersson, L. C. (2007). Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart. American Journal of Physiology. Heart and Circulatory Physiology, 293(3), H1766–H1771. https://doi.org/10.1152/ajpheart.00017.2007

    Article  CAS  PubMed  Google Scholar 

  50. Chen, R. C., Sun, G. B., Ye, J. X., Wang, J., Zhang, M. D., & Sun, X. B. (2017). Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3 and TRPC6 mediated Ca2+ overload in rat cardiomyocytes. Toxicology Letters, 276, 21–30. https://doi.org/10.1016/j.toxlet.2017.04.010

    Article  CAS  PubMed  Google Scholar 

  51. Takada, A., Miki, T., Kuno, A., Kouzu, H., Sunaga, D., Itoh, T., Tanno, M., Yano, T., Sato, T., Ishikawa, S., & Miura, T. (2012). Role of ER stress in ventricular contractile dysfunction in type 2 diabetes. PLoS One, 7(6), e39893. https://doi.org/10.1371/journal.pone.0039893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wu, X. D., Zhang, Z. Y., Sun, S., Li, Y. Z., Wang, X. R., Zhu, X. Q., Li, W. H., & Liu, X. H. (2013). Hypoxic preconditioning protects microvascular endothelial cells against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress. Apoptosis : An International Journal on Programmed Cell Death, 18(1), 85–98. https://doi.org/10.1007/s10495-012-0766-6

    Article  CAS  PubMed  Google Scholar 

  53. Wang, J., Wu, Y., Yuan, F., Liu, Y., Wang, X., Cao, F., Zhang, Y., & Wang, S. (2016). Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats. Life Sciences, 160, 57–63. https://doi.org/10.1016/j.lfs.2016.07.002

    Article  CAS  PubMed  Google Scholar 

  54. Hamstra, S. I., Whitley, K. C., Baranowski, R. W., Kurgan, N., Braun, J. L., Messner, H. N., & Fajardo, V. A. (2020). The role of phospholamban and GSK3 in regulating rodent cardiac SERCA function. American Journal of Physiology. Cell Physiology, 319(4), C694–C699. https://doi.org/10.1152/ajpcell.00318.2020

    Article  CAS  PubMed  Google Scholar 

  55. Tscheschner, H., Meinhardt, E., Schlegel, P., Jungmann, A., Lehmann, L. H., Müller, O. J., Most, P., Katus, H. A., & Raake, P. W. (2019). CaMKII activation participates in doxorubicin cardiotoxicity and is attenuated by moderate GRP78 overexpression. PLoS One, 14(4), e0215992. https://doi.org/10.1371/journal.pone.0215992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Anderson, M. E., Brown, J. H., & Bers, D. M. (2011). CaMKII in myocardial hypertrophy and heart failure. Journal of Molecular and Cellular Cardiology, 51(4), 468–473. https://doi.org/10.1016/j.yjmcc.2011.01.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhang, T., Zhang, Y., Cui, M., **, L., Wang, Y., Lv, F., Liu, Y., Zheng, W., Shang, H., Zhang, J., Zhang, M., Wu, H., Guo, J., Zhang, X., Hu, X., Cao, C. M., & **ao, R. P. (2016). CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nature Medicine, 22(2), 175–182. https://doi.org/10.1038/nm.4017

    Article  CAS  PubMed  Google Scholar 

  58. Rajtik, T., Carnicka, S., Szobi, A., Giricz, Z., O-Uchi, J., VHassova, Svec, P., Ferdinandy, P., Ravingerova, T., & Adameova, A. (2016). Oxidative activation of CaMKIIδ in acute myocardial ischemia/reperfusion injury: A role of angiotensin AT1 receptor-NOX2 signaling axis. European Journal of Pharmacology, 771, 114–122. https://doi.org/10.1016/j.ejphar.2015.12.024

    Article  CAS  PubMed  Google Scholar 

  59. Szobi, A., Rajtik, T., Carnicka, S., Ravingerova, T., & Adameova, A. (2014). Mitigation of postischemic cardiac contractile dysfunction by CaMKII inhibition: Effects on programmed necrotic and apoptotic cell death. Molecular and Cellular Biochemistry, 388(1–2), 269–276. https://doi.org/10.1007/s11010-013-1918-x

    Article  CAS  PubMed  Google Scholar 

  60. Koncsos, G., Varga, Z. V., Baranyai, T., Boengler, K., Rohrbach, S., Li, L., Schlüter, K. D., Schreckenberg, R., Radovits, T., Oláh, A., Mátyás, C., Lux, Á., Al-Khrasani, M., Komlódi, T., Bukosza, N., Máthé, D., Deres, L., Barteková, M., Rajtík, T., Adameová, A., … Ferdinandy, P. (2016). Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress. American journal of physiology. Heart and circulatory physiology, 311(4), H927–H943. https://doi.org/10.1152/ajpheart.00049.2016.

  61. Woolums, B. M., McCray, B. A., Sung, H., Tabuchi, M., Sullivan, J. M., Ruppell, K. T., Yang, Y., Mamah, C., Aisenberg, W. H., Saavedra-Rivera, P. C., Larin, B. S., Lau, A. R., Robinson, D. N., **ang, Y., Wu, M. N., Sumner, C. J., & Lloyd, T. E. (2020). TRPV4 disrupts mitochondrial transport and causes axonal degeneration via a CaMKII-dependent elevation of intracellular Ca2. Nature Communications, 11(1), 2679. https://doi.org/10.1038/s41467-020-16411-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang, S., Lu, K., Yang, S., Wu, Y., Liao, J., Lu, Y., Wu, Q., Zhao, N., Dong, Q., Chen, L., & Du, Y. (2021). Activation of transient receptor potential vanilloid 4 exacerbates myocardial ischemia-reperfusion injury via JNK-CaMKII phosphorylation pathway in isolated mice hearts. Cell Calcium, 100, 102483. https://doi.org/10.1016/j.ceca.2021.102483

    Article  CAS  PubMed  Google Scholar 

  63. Adapala, R. K., Kanugula, A. K., Paruchuri, S., Chilian, W. M., & Thodeti, C. K. (2020). TRPV4 deletion protects heart from myocardial infarction-induced adverse remodeling via modulation of cardiac fibroblast differentiation. Basic Research in Cardiology, 115(2), 14. https://doi.org/10.1007/s00395-020-0775-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Horton, J. S., Buckley, C. L., & Stokes, A. J. (2013). Successful TRPV1 antagonist treatment for cardiac hypertrophy and heart failure in mice. Channels (Austin, Tex.), 7(1), 17–22. https://doi.org/10.4161/chan.23006

    Article  CAS  PubMed  Google Scholar 

  65. Iwata, Y., Wakabayashi, S., Ito, S., & Kitakaze, M. (2020). Production of TRPV2-targeting functional antibody ameliorating dilated cardiomyopathy and muscular dystrophy in animal models. Laboratory Investigation; A Journal of Technical Methods and Pathology, 100(2), 324–337. https://doi.org/10.1038/s41374-019-0363-1

    Article  CAS  PubMed  Google Scholar 

  66. Zhang, Q., Qi, H., Cao, Y., Shi, P., Song, C., Ba, L., Chen, Y., Gao, J., Li, S., Li, B., & Sun, H. (2018). Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats. Journal of Cellular and Molecular Medicine, 22(12), 6055–6067. https://doi.org/10.1111/jcmm.13880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research was supported by the Faculty of Pharmacy, Comenius University, Bratislava [FaF UK/13/2021]; Scientific Grant Agency of The Ministry of Education of Slovak Republic [VEGA 1/0775/21 and 2/0151/17]; and the Slovak Research And Development Agency [APVV-15-0607].

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia

    Peter Galis, Linda Bartosova, Adrian Szobi, Csaba Horvath, Adriana Adameova & Tomas Rajtik

  2. Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04, Bratislava, Slovakia

    Veronika Farkasova, Adriana Adameova & Tomas Rajtik

  3. Faculty of Medicine, Institute of Pathophysiology, Comenius University, Špitálska 24, 813 72, Bratislava, Slovakia

    Dominika Kovacova

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  1. Peter Galis
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Contributions

Conceptualization, TR, VF, AS and AD-A; writing—original draft preparation, PG, LB, TR; writing—review and editing, PG; TR, LB, VF, CH, DK and AD-A; visualization, TR, LB, and PG; supervision, TR, VF, CH; project administration, TR, VF, DK and AD-A; funding acquisition, TR, VF and AD-A, performing experiments, TR, PG, LB, and DK. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tomas Rajtik.

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Ethical Approval

All procedures conform to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication No. 85‐23, revised 1996) and have been authorized by the ethical commission of the Institute of Experimental Pharmacology and Toxicology of the Slovak Academy of Sciences and State Veterinary and Food Administration of the Slovak Republic (No. 1972/17-221).

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Galis, P., Bartosova, L., Farkasova, V. et al. Intermittent Hypoxic Preconditioning Plays a Cardioprotective Role in Doxorubicin-Induced Cardiomyopathy. Cardiovasc Toxicol 23, 185–197 (2023). https://doi.org/10.1007/s12012-023-09793-7

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