Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Vascular endothelial dysfunction after anthracyclines treatment in children with acute lymphoblastic leukemia

  • Jang, Woo Jung (Department of Pediatrics, Graduate School of Medicine, Gachon University) ;
  • Choi, Duk Yong (Department of Pediatrics, Graduate School of Medicine, Gachon University) ;
  • Jeon, In-Sang (Department of Pediatrics, Graduate School of Medicine, Gachon University)
  • Received : 2012.08.03
  • Accepted : 2012.10.22
  • Published : 2013.03.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Anthracyclines have been utilized in the treatment of children with acute lymphoblastic leukemia (ALL). Recent studies have shown that anthracyclines may induce toxicity in the vascular endothelium. This study was performed using brachial artery reactivity (BAR) to evaluate vascular endothelial function in ALL patients who were treated with anthracycline chemotherapy. Methods: We included 21 children with ALL who received anthracycline chemotherapy and 20 healthy children. The cumulative dose of anthracyclines in the ALL patients was $142.5{\pm}18.2/m^2$. The last anthracycline dose was administered to the patients 2 to 85 months prior to their examination using BAR. The diameter of the brachial artery was measured in both groups using echocardiography, and BAR was calculated as the percentage change in the arterial diameter after release of the cuff relative to the baseline vessel diameter. Results: In the anthracycline-treated group, BAR was observed to be $3.4%{\pm}3.9%$, which was significantly lower than that observed in the control group ($12.1%{\pm}8.0%$, P<0.05). The time elapsed after the last anthracycline treatment and the age at the time of treatment did not affect the change in BAR (P =0.06 and P =0.13, respectively). Conclusion: These results provided evidence that treatment of ALL patients with anthracycline results in endothelial dysfunction. A larger cohort study and a longer follow-up period will be required to clarify the relationship between endothelial dysfunction resulting from anthracycline treatment for childhood ALL and occurrence of cardiovascular diseases later in life.

Keywords

References

  1. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006;354:166-78. https://doi.org/10.1056/NEJMra052603
  2. Bhatia S. Late effects among survivors of leukemia during childhood and adolescence. Blood Cells Mol Dis 2003;31:84-92. https://doi.org/10.1016/S1079-9796(03)00072-X
  3. Hatzipantelis ES, Athanassiou-Metaxa M, Gombakis N, Tzimouli V, Taparkou A, Sidi-Fragandrea V, et al. Thrombomodulin and von Willebrand factor: relation to endothelial dysfunction and disease outcome in children with acute lymphoblastic leukemia. Acta Haematol 2011;125:130-5. https://doi.org/10.1159/000322120
  4. Duquaine D, Hirsch GA, Chakrabarti A, Han Z, Kehrer C, Brook R, et al. Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase. Vasc Med 2003; 8:101-7. https://doi.org/10.1191/1358863x03vm476oa
  5. Chow AY, Chin C, Dahl G, Rosenthal DN. Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study. J Clin Oncol 2006;24:925-8. https://doi.org/10.1200/JCO.2005.03.5956
  6. Vita JA. Endothelial function. Circulation 2011;124:e906-12. https://doi.org/10.1161/CIRCULATIONAHA.111.078824
  7. Corretti M. Brachial artery reactivity: clinical tool or research toy? J Am Soc Echocardiogr 2004;17:693-6. https://doi.org/10.1016/j.echo.2004.03.016
  8. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002;39:257-65.
  9. Lieberman EH, Gerhard MD, Uehata A, Selwyn AP, Ganz P, Yeung AC, et al. Flow-induced vasodilation of the human brachial artery is impaired in patients <40 years of age with coronary artery disease. Am J Cardiol 1996;78:1210-4. https://doi.org/10.1016/S0002-9149(96)00597-8
  10. Pui CH, Pei D, Sandlund JT, Campana D, Ribeiro RC, Razzouk BI, et al. Risk of adverse events after completion of therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 2005;23: 7936-41. https://doi.org/10.1200/JCO.2004.01.0033
  11. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801-9. https://doi.org/10.1038/362801a0
  12. Murata T, Yamawaki H, Yoshimoto R, Hori M, Sato K, Ozaki H, et al. Chronic effect of doxorubicin on vascular endothelium assessed by organ culture study. Life Sci 2001;69:2685-95. https://doi.org/10.1016/S0024-3205(01)01352-2
  13. Vásquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B. Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry 1997;36: 11293-7. https://doi.org/10.1021/bi971475e
  14. Kalivendi SV, Kotamraju S, Zhao H, Joseph J, Kalyanaraman B. Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and calcium. J Biol Chem 2001;276:47266- https://doi.org/10.1074/jbc.M106829200
  15. Wu S, Ko YS, Teng MS, Ko YL, Hsu LA, Hsueh C, et al. Adriamycininduced cardiomyocyte and endothelial cell apoptosis: in vitro and in vivo studies. J Mol Cell Cardiol 2002;34:1595-607. https://doi.org/10.1006/jmcc.2002.2110
  16. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26:1235-41. https://doi.org/10.1016/0735-1097(95)00327-4
  17. Oudin C, Simeoni MC, Sirvent N, Contet A, Begu-Le Coroller A, Bordigoni P, et al. Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood 2011; 117:4442-8. https://doi.org/10.1182/blood-2010-09-304899

Cited by

  1. Treatment, Behavioral, and Psychosocial Components of Cardiovascular Disease Risk Among Survivors of Childhood and Young Adult Cancer vol.4, pp.4, 2013, https://doi.org/10.1161/jaha.115.001891
  2. Upregulation of peroxiredoxin III in doxorubicin-induced cytotoxicity and the FoxO3a-dependent expression in H9c2 cardiac cells vol.10, pp.4, 2015, https://doi.org/10.3892/etm.2015.2693
  3. A Review of Cardiorespiratory Fitness in Adolescent and Young Adult Survivors of Childhood Cancer: Factors that Affect its Decline and Opportunities for Intervention vol.5, pp.1, 2013, https://doi.org/10.1089/jayao.2015.0031
  4. Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells vol.13, pp.1, 2013, https://doi.org/10.3892/mmr.2015.4544
  5. Vascular toxic effects of cancer therapies vol.17, pp.8, 2013, https://doi.org/10.1038/s41569-020-0347-2
  6. Anthracycline-Induced Cardiotoxicity: The Role of Endothelial Dysfunction vol.146, pp.3, 2013, https://doi.org/10.1159/000512771
  7. Anthracycline-Induced Cardiotoxicity: The Role of Endothelial Dysfunction vol.146, pp.3, 2013, https://doi.org/10.1159/000512771
  8. Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence vol.221, pp.None, 2013, https://doi.org/10.1016/j.pharmthera.2020.107751
  9. Life after Cell Death-Survival and Survivorship Following Chemotherapy vol.13, pp.12, 2013, https://doi.org/10.3390/cancers13122942
  10. Premature Ocular Aging Features in Childhood Acute Lymphoblastic Leukemia Survivors vol.10, pp.4, 2021, https://doi.org/10.1089/jayao.2020.0064
  11. Endothelial Dysfunction in Childhood Cancer Survivors: A Narrative Review vol.12, pp.1, 2013, https://doi.org/10.3390/life12010045