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Expression of Flk-1 and Cyclin D2 mRNA in the Myocardium of Rats with Doxorubicin-Induced Cardiomyopathy and after Treatment with Betulonic Acid Amide

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Bulletin of Experimental Biology and Medicine Aims and scope

The expression of VEGFR2 (Flk-1, according to immunohistochemistry) and of cyclin D2 mRNA (according to real-time PCR) in the myocardium of rats is studied in doxorubicin-induced cardiomyopathy and in response to betulonic acid amide. Doxorubicin alone and in combination with betulonic acid amide causes after 3 days a manifest reduction of cyclin D2 mRNA expression (by 38 and 63%, respectively), while injection of betulonic acid amide alone causes a 23-fold increase of cyclin D2 mRNA expression. An increase of cyclin D2 mRNA expression has been detected in all experimental groups after 14 days of experiment, the most pronounced in response to betulonic acid amide (63 times). The expression of Flk-1 in cardiomyocytes increases significantly in response to both chemical agents starting from day 3 of experiment. These results indicate that doxorubicin and betulonic acid amide induce cytoprotective reactions in the myocardium, first at the intracellular, then at the cellular levels.

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References

  1. Klinnikova MG, Lushnikova EL, Koldysheva EV, Tolstikova TG, Sorokina IV, Yuzhik EI, Mzhelskaya MM. Cardiotoxic and Dyslipidemic Effects of Doxorubicin and Betulinic Acid Amide. Bull. Exp. Biol. Med. 2016;162(2):277-282.

    Article  CAS  PubMed  Google Scholar 

  2. Ahuja P, Sdek P, MacLellan WR. Cardiac myocyte cell cycle control in development, disease, and regeneration. Physiol. Rev. 2007;87(2):521-544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Busk PK, Hinrichsen R, Bartkova J, Hansen AH, Christoffersen TE, Bartek J, Haunsø S. Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy. Exp. Cell Res. 2005;304(1):149-161.

    Article  CAS  PubMed  Google Scholar 

  4. Chen XG, Lv YX, Zhao D, Zhang L, Zheng F, Yang JY, Li XL, Wang L, Guo LY, Pan YM, Yan YW, Chen SY, Wang JN, Tang JM, Wan Y. Vascular endothelial growth factor-C protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis. Mol. Cell. Biochem. 2016 Vol. 413(1-2):9-23.

    Article  CAS  PubMed  Google Scholar 

  5. Chen Y, Amende I, Hampton TG, Yang Y, Ke Q, Min JY, Xiao YF, Morgan JP. Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells. Am. J. Physiol. Heart Circ. Physiol. 2006;291(4):H1653-H1658.

    Article  CAS  PubMed  Google Scholar 

  6. Gay MS, Dasgupta C, Li Y, Kanna A, Zhang L. Dexamethasone induces cardiomyocyte terminal differentiation via epigenetic repression of cyclin D2 gene. J. Pharmacol. Exp. Ther. 2016;358(2):190-198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kushner JA, Ciemerych MA, Sicinska E, Wartschow LM, Teta M, Long SY, Sicinski P, White MF. Cyclins D2 and D1 are essential for postnatal pancreatic cell growth. Moll. Cell. Biol. 2005;25(9):3752-3762.

    Article  CAS  Google Scholar 

  8. Laflamme MA, Murry C.E. Heart regeneration. Nature. 2011;473:326-335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mollova M, Bersell K, Walsh S, Savla J, Das LT, Park SY, Silberstein LE, Dos Remedios CG, Graham D, Colan S, Kühn B. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc. Natl Acad. Sci. USA. 2013;110(4):1446-1451.

  10. Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J. Mol. Cell. Cardiol. 2012;52(6):1213-1225.

    Article  CAS  PubMed  Google Scholar 

  11. Polizzotti BD, Ganapathy B, Walsh S, Choudhury S, Ammanamanchi N, Bennett DG, dos Remedios CG, Haubner BJ, Penninger JM, Kühn B. Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window. Sci. Transl. Med. 2015;7(281):281ra45. doi: https://doi.org/10.1126/scitranslmed.aaa5171.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Pasumarthi KB, Nakajima H, Nakajima HO, Soonpaa MH, Field LJ. Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice. Circ. Res. 2005;96(1):110-118.

    Article  CAS  PubMed  Google Scholar 

  13. Sallinen P, Mänttäri S, Leskinen H, Ilves M, Ruskoaho H, Saarela S. Time course of changes in the expression of DHPR, RyR(2), and SERCA2 after myocardial infarction in the rat left ventricle. Mol. Cell. Biochem. 2007;303(1-2):97-103.

  14. Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res. 2002;90(12):1243-1250.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang YW, Shi J, Li YJ, Wei L. Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Arch. Immunol. Ther. Exp. (Warsz). 2009;57(6):435-445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to M. M. Mzhelskaya.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 163, No. 6, pp. 778-783, June, 2017

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Mzhelskaya, M.M., Klinnikova, M.G., Koldysheva, E.V. et al. Expression of Flk-1 and Cyclin D2 mRNA in the Myocardium of Rats with Doxorubicin-Induced Cardiomyopathy and after Treatment with Betulonic Acid Amide. Bull Exp Biol Med 163, 809–813 (2017). https://doi.org/10.1007/s10517-017-3909-5

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  • DOI: https://doi.org/10.1007/s10517-017-3909-5

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