Cor Vasa 2022, 64(4):390-397 | DOI: 10.33678/cor.2022.046

The human hypoxia-inducible factor 1alpha gene in anthracycline-induced heart failure

Kristina V. Kopevaa, Elena V. Grakovaa, Sergey N. Shilovb, Ekaterina N. Berezikovab, Anna A.Popovab, Maria N. Neupokoevab, Elena T. Ratushnyakb, Alexander T. Teplyakova
a Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Department of Myocardial Pathology, Tomsk, Russian Federation
b Novosibirsk State Medical University, Department of Pathological Physiology and Clinical Pathophysiology, Novosibirsk, Russian Federation

Objective: The objective of the study was to evaluate the role of hypoxia-inducible factor 1alpha (HIF1A) gene (1772C>T, rs11549465) in the course of anthracycline-induced heart failure (AIHF) in women without previous cardiovascular diseases (CVD) during 24 months.

Methods: A total of 114 women, median age of 47.0 (44.0; 52.0) years with AIHF of NYHA class I-III who received doxorubicin for breast cancer were enrolled. Evaluation of gene polymorphisms was carried out by polymerase chain reaction at baseline.

Results: After 24 months of follow-up all patients had breast cancer remission and were divided into 2 groups: group 1 comprised women with adverse course of AIHF (n = 36), group 2 comprised those without it (n = 75). The presence of C/T genotype of HIF1A gene (1772C>T, rs11549465) (OR = 3.65; p = 0.009) was related with adverse course of AIHF. Women with C/T genotype of HIF1A gene (1772C>T, rs11549465) had further progression of AIHF: left ventricle ejection fraction significantly (p <0.001) decreased by 11.8% from 51 (47; 53) to 45 (43; 46)%, end-systolic dimension increased by 7.8% (p <0.001), and end-diastolic dimension by 5.2% (p <0.001).

Conclusion: Polymorphism of C/T of hypoxia-inducible factor 1alpha gene (1772C>T, rs11549465) in women without previous CVD was associated with adverse course of AIHF during 24 months.

Keywords: Anthracycline-induced heart failure, Genes, Hypoxia-inducible factor 1alpha, Polymorphism, Prognosis

Received: December 28, 2021; Revised: December 28, 2021; Accepted: April 26, 2022; Published: September 1, 2022  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Kopeva KV, Grakova EV, Shilov SN, Berezikova EN, Popova AA, Neupokoeva MN, et al.. The human hypoxia-inducible factor 1alpha gene in anthracycline-induced heart failure. Cor Vasa. 2022;64(4):390-397. doi: 10.33678/cor.2022.046.
Download citation

References

  1. Feijen EAML, Font-Gonzalez A, Van der Pal HJH, et al. Risk and Temporal Changes of Heart Failure Among 5-Year Childhood Cancer Survivors: a DCOG-LATER Study. J Am Heart Assoc 2019;8:e009122. Go to original source... Go to PubMed...
  2. Bodley A, Liu LF, Israel M, Seshadri R, et al. DNA topoisomerase II-mediated interaction of doxorubicin and daunorubicin congeners with DNA. Cancer Res 1989;49:5969-5978.
  3. Lyu YL, Lin CP, Azarova AM, et al. Role of topoisomerase 2beta in the expression of developmentally regulated genes. Mol Cell Biol 2006;26:7929-7941. Go to original source... Go to PubMed...
  4. Tanaka T, Yamaguchi J, Shoji K, Nangaku M. Anthracycline inhibits recruitment of hypoxia-inducible transcription factors and suppresses tumor cell migration and cardiac angiogenic response in the host. J Biol Chem 2012;287:34866-34882. Go to original source... Go to PubMed...
  5. Sato M, Hirose K, Ichise K, et al. Not Only Hypoxia- but Radiation-Induced Epithelial-Mesenchymal Transition Is Modulated by Hypoxia-Inducible Factor 1 in A549 Lung Cancer Cells. Folia Biol (Praha) 2021;67:62-69. Go to original source... Go to PubMed...
  6. Packer M. Mutual Antagonism of Hypoxia-Inducible Factor Isoforms in Cardiac, Vascular, and Renal Disorders. JACC Basic Transl Sci 2020;5:961-968. Go to original source... Go to PubMed...
  7. Krishnan J, Suter M, Windak R, et al. Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab 2009;9:512-524. Go to original source... Go to PubMed...
  8. Pan Y, Mansfield KD, Bertozzi CC, et al. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol 2007;27:912-925. Go to original source... Go to PubMed...
  9. Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 2012;18:1639-1642. Go to original source... Go to PubMed...
  10. Chen Y, Jungsuwadee P, Vore M, et al. Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol Interv 2007;7:147-156. Go to original source... Go to PubMed...
  11. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021;42:373-498. Go to original source... Go to PubMed...
  12. Strauss E, Waliszewski K, Oszkinis G, Staniszewski R. Polymorphisms of genes involved in the hypoxia signaling pathway and the development of abdominal aortic aneurysms or large-artery atherosclerosis. J Vasc Surg 2015;61:1105-1113. Go to original source... Go to PubMed...
  13. Chandel NS, McClintock DS, Feliciano CE, et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 2000;275:25130-25138. Go to original source... Go to PubMed...
  14. Zhang H, Gao P, Fukuda R, et al. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 2007;11:407-420. Go to original source... Go to PubMed...
  15. Schönenberger MJ, Kovacs WJ. Hypoxia signaling pathways: modulators of oxygen-related organelles. Front Cell Dev Biol 2015;3:42. Go to original source... Go to PubMed...
  16. Walter KM, Schönenberger MJ, Trötzmüller M, et al. Hif-2a promotes degradation of mammalian peroxisomes by selective autophagy. Cell Metab 2014;20:882-897. Go to original source... Go to PubMed...
  17. Salvatorelli E, Guarnieri S, Menna P, et al. Defective one- or two-electron reduction of the anticancer anthracyclineepirubicin in human heart. Relative importance of vesicular sequestration and impaired efficiency of electron addition. J Biol Chem 2006;281:10990-11001. Go to original source... Go to PubMed...
  18. Lee K, Qian DZ, Rey S, et al. Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc Natl Acad Sci USA 2009;106:2353-2358. Go to original source... Go to PubMed...
  19. Pu J, Zhu S, Zhou D, et al. Propofol alleviates apoptosis induced by chronic high glucose exposure via regulation of HIF-1a in H9c2 cells. Oxid Med Cell Longev 2019;2019:4824035. Go to original source... Go to PubMed...
  20. Hölscher M, Schäfer K, Krull S, et al. Unfavourable consequences of chronic cardiac HIF-1A stabilization. Cardiovasc Res 2012;94:77-86. Go to original source... Go to PubMed...
  21. Pohl J, Hendgen-Cotta UB, Stock P, et al. Myocardial expression of macrophage migration inhibitory factor in patients with heart failure. J Clin Med 2017;6:95. Go to original source... Go to PubMed...
  22. Li G, Lu WH, Wu XW, et al. Admission hypoxiainducible factor 1a levels and in-hospital mortality in patients withacute decompensated heart failure. BMC Cardiovasc Disord. 2015;15:79. Go to original source... Go to PubMed...
  23. Marfella R, Esposito K, Nappo F, et al. Expression of angiogenic factors during acute coronary syndromes in human type 2 diabetes. Diabetes 2004;53:2383-2391. Go to original source... Go to PubMed...
  24. Willam C, Maxwell PH, Nichols L, et al. HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligation. J Mol Cell Cardiol 2006;41:68-77. Go to original source... Go to PubMed...
  25. Warbrick I, Rabkin SW. Hypoxia-inducible factor 1-alpha (HIF-1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction. Obes Rev 2019;20:701-712. Go to original source... Go to PubMed...
  26. Sharma NM, Cunningham CJ, Zheng H, et al. Hypoxia-Inducible Factor-1α Mediates Increased Sympathoexcitation via Glutamatergic N-Methyl-d-Aspartate Receptors in the Paraventricular Nucleus of Rats With Chronic Heart Failure. Circ Heart Fail 2016;9:e003423. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.





Cor et Vasa

You are accessing a site intended for medical professionals, not the lay public. The site may also contain information that is intended only for persons authorized to prescribe and dispense medicinal products for human use.

I therefore confirm that I am a healthcare professional under Act 40/1995 Coll. as amended by later regulations and that I have read the definition of a healthcare professional.