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Arsenic-Induced Cardiovascular Diseases and their Correlation with Mitochondrial DNA Copy Number, Deletion, and Telomere Length in Bangladeshi Population

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Abstract

Arsenic contamination is a global health concern, primarily through contaminated groundwater and its entry into the food chain. The association between arsenic exposure and cardiovascular diseases (CVDs) is particularly alarming due to CVDs being the leading cause of death worldwide. Arsenic exposure has also been linked to changes in telomere length, mitochondrial DNA copy number (mtDNAcn), and deletion, further increasing the risk of CVDs. We aimed to determine whether arsenic exposure alters telomere length and mtDNAcn and deletion in a total of 50 CVD patients who underwent open heart surgery hailed from known arsenic-affected and unaffected areas in Bangladesh. Amount of arsenic was determined from the collected nails and cardiac tissues. Relative telomere length and mtDNAcn and deletion were quantified by qRT-PCR. The patients from arsenic-contaminated areas had higher average arsenic deposits in their fingers and toenails (P < 0.05) and higher cardiac tissue injury scores (P < 0.05). Moreover, approximately 1.5-fold shorter telomere length (P < 0.05, r =  − 0.775), 1.2-fold decreased mtDNAcn (P < 0.05, r = − 0.797), and an 81-fold higher amount of mitochondrial DNA deletion (P < 0.05, r = 0.784) were observed in the patients who had higher arsenic deposition in their nails. Higher levels of arsenic exposure were found to be linked to shorter telomere length, decreased mtDNAcn, and increased mitochondrial DNA deletion in the patients from As-affected areas. It can also be anticipated that the correlation of arsenic exposure with telomere length, mtDNAcn, and deletion can be used as biomarkers for early diagnosis of arsenic-induced cardiovascular diseases.

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References

  1. Mandal, B. K., & Suzuki, K. T. (2002). Arsenic round the world: A review. Talanta, 58(1), 201–235.

    Article  CAS  PubMed  Google Scholar 

  2. Ahsan, H., Chen, Y., Liu, X., Siddique, A. B., Wu, T., Roy, S., Van Geen, K., Slavkovich, V., Levy, D., Factor-Litvak, P., Selhub, J., Gamble, M., Jorgensen, I., & Graziano, J. H. (2007). Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions in Bangladesh. Cancer Epidemiology Biomarkers and Prevention, 16(6), 1270–1278. https://doi.org/10.1158/1055-9965.EPI-06-0676

    Article  CAS  Google Scholar 

  3. Navas-Acien, A., Sharrett, A. R., Silbergeld, E. K., Schwartz, B. S., Nachman, K. E., Burke, T. A., & Guallar, E. (2005). Arsenic exposure and cardiovascular disease: A systematic review of the epidemiologic evidence. American Journal of Epidemiology, 162(11), 1037–1049. https://doi.org/10.1093/aje/kwi330

    Article  PubMed  Google Scholar 

  4. Xu, L., Mondal, D., & Polya, D. A. (2020). Positive association of cardiovascular disease (CVD) with chronic exposure to drinking water arsenic (As) at concentrations below the WHO provisional guideline value: A systematic review and meta-analysis. International Journal of Environmental Research and Public Health, 17(7), 2536. https://doi.org/10.3390/ijerph17072536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen, Y., Graziano, J. H., Parvez, F., Liu, M., Slavkovich, V., Kalra, T., Argos, M., Islam, T., Ahmed, A., Rakibuz-Zaman, M., Hasan, R., Sarwar, G., Levy, D., van Geen, A., Graziano, J. H., & Ahsan, H. (2013). A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh. Environmental Health Perspectives, 121(7), 832–838. https://doi.org/10.1289/ehp.1205797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rhyu, M. S. (1995). Telomeres, telomerase, and immortality. Journal of the National Cancer Institute, 87(12), 884–894. https://doi.org/10.1093/jnci/87.12.884

    Article  CAS  PubMed  Google Scholar 

  7. Saliques, S., Zeller, M., Lorin, J., Lorgis, L., Teyssier, J. R., Cottin, Y., & Rochette, L. (2010). Telomere length and cardiovascular disease. Archives of Cardiovascular Diseases, 103(8–9), 454–459. https://doi.org/10.1016/j.acvd.2010.08.002

    Article  PubMed  Google Scholar 

  8. Yeh, J. K., & Wang, C. Y. (2016). Telomeres and telomerase in cardiovascular diseases. Genes (Basel), 7(9), 58. https://doi.org/10.3390/genes7090058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Khaleda, L., Al-Forkan, M., Wali, F. B., Alam, M. J., Datta, A., Shawon, I. I., Hosain, N., & Rahman, M. Z. (2019). Effect of arsenic exposure on human telomerase reverse transcriptase (hTERT) gene expression: Risk of cardiovascular diseases: Arsenic exposure and cardiovascular diseases. Bangladesh Medical Research Council Bulletin, 45(1), 3–10. https://doi.org/10.3329/bmrcb.v45i1.41802

    Article  Google Scholar 

  10. Bouffler, S. D., Blasco, M. A., Cox, R., & Smith, P. J. (2001). Telomeric sequences, radiation sensitivity and genomic instability. International Journal of Radiation Biology, 77(10), 995–1005. https://doi.org/10.1080/0955300011006932

    Article  CAS  PubMed  Google Scholar 

  11. Shay, J. W., Zou, Y., Hiyama, E., & Wright, W. E. (2001). Telomerase and cancer. Human molecular genetics, 10(7), 677–685. https://doi.org/10.1093/hmg/10.7.677

    Article  CAS  PubMed  Google Scholar 

  12. Gao, J., Roy, S., Tong, L., Argos, M., Jasmine, F., Rahaman, R., Rakibuz-Zaman, M., Parvez, F., Ahmed, A., Hore, S. K., Sarwar, G., Slavkovich, V., Yunus, M., Rahman, M., Baron, J. A., Graziano, J. H., Ahsan, H., & Pierce, B. L. (2015). Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals. Environmental Research, 136, 462–469. https://doi.org/10.1016/j.envres.2014.09.040

    Article  CAS  PubMed  ADS  Google Scholar 

  13. Ameer, S. S., Xu, Y., Engström, K., Li, H., Tallving, P., Nermell, B., Boemo, A., Parada, L. A., Peñaloza, L. G., Concha, G., Harari, F., Vahter, M., & Broberg, K. (2016). Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood. Frontiers in Cell and Developmental Biology. https://doi.org/10.3389/fcell.2016.00087

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ferrario, D., Collotta, A., Carfi, M., Bowe, G., Vahter, M., Hartung, T., & Gribaldo, L. (2009). Arsenic induces telomerase expression and maintains telomere length in human cord blood cells. Toxicology, 260(1–3), 132–141. https://doi.org/10.1016/j.tox.2009.03.019

    Article  CAS  PubMed  Google Scholar 

  15. Zhang, T. C., Schmitt, M. T., & Mumford, J. L. (2003). Effects of arsenic on telomerase and telomeres in relation to cell proliferation and apoptosis in human keratinocytes and leukemia cells in vitro. Carcinogenesis, 24(11), 1811–1817. https://doi.org/10.1093/carcin/bgg141

    Article  CAS  PubMed  Google Scholar 

  16. Yue, P., Jing, S., Liu, L., Ma, F., Zhang, Y., Wang, C., Duan, H., Zhou, K., Hua, Y., Wu, G., & Li, Y. (2018). Association between mitochondrial DNA copy number and cardiovascular disease: Current evidence based on a systematic review and meta-analysis. PLoS One, 13(11), e0206003. https://doi.org/10.1371/journal.pone.0206003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Clay Montier, L. L., Deng, J. J., & Bai, Y. (2009). Number matters: Control of mammalian mitochondrial DNA copy number. Journal of Genetics and Genomics, 36(3), 125–131. https://doi.org/10.1016/S1673-8527(08)60099-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wallace, D. C. (2008). Mitochondria as Chi. Genetics, 179(2), 727–735. https://doi.org/10.1534/genetics.104.91769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bayeva, M., Gheorghiade, M., & Ardehali, H. (2013). Mitochondria as a therapeutic target in heart failure. Journal of the American College of Cardiology, 61(6), 599–610. https://doi.org/10.1016/j.jacc.2012.08.1021

    Article  CAS  PubMed  Google Scholar 

  20. Fu, C., Chen, W., & Jin, Y. (2016). The complete mitochondrial genome of Phrynocephalus guinanensis (Reptilia, Squamata, Agamidae). Mitochondrial DNA, 27(2), 1103–1104. https://doi.org/10.3109/19401736.2014.933320

    Article  CAS  PubMed  Google Scholar 

  21. Taylor, R. W., & Turnbull, D. M. (2005). Mitochondrial DNA mutations in human disease. Nature Reviews Genetics, 6(5), 389–402. https://doi.org/10.1038/nrg1606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Campa, D., Barrdahl, M., Santoro, A., Severi, G., Baglietto, L., Omichessan, H., Tumino, R., Bueno-de-Mesquita, H. B., Peeters, P. H., Weiderpass, E., Chirlaque, M. D., Rodríguez-Barranco, M., Agudo, A., Gunter, M., Dossus, L., Krogh, V., Matullo, G., Trichopoulou, A., Travis, R. C., … Kaaks, R. (2018). Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European prospective investigation into cancer and nutrition (EPIC) study. Breast Cancer Research. https://doi.org/10.1186/s13058-018-0955-5

    Article  PubMed  PubMed Central  Google Scholar 

  23. Phillips, N. R., Sprouse, M. L., & Roby, R. K. (2014). Simultaneous quantification of mitochondrial DNA copy number and deletion ratio: A multiplex real-time PCR assay. Scientific Reports. https://doi.org/10.1038/srep03887

    Article  PubMed  PubMed Central  Google Scholar 

  24. Datta, A., Alam, M. J., Khaleda, L., & Al-Forkan, M. (2021). Protective effects of Corchorus olitorius and Butea monosperma against Arsenic induced aberrant methylation and mitochondrial DNA damage in Wistar rat model. Toxicology Reports, 8, 30–37. https://doi.org/10.1016/j.toxrep.2020.12.017

    Article  CAS  PubMed  Google Scholar 

  25. Zheng, J., Huang, T., Yu, Y., Hu, X., Yang, B., & Li, D. (2012). Fish consumption and CHD mortality: An updated meta-analysis of seventeen cohort studies. Public Health Nutrition, 15(4), 725–737. https://doi.org/10.1017/S1368980011002254

    Article  PubMed  Google Scholar 

  26. Al-Forkan, M., Wali, F. B., Khaleda, L., Alam, M. J., Chowdhury, R. H., Datta, A., Rahman, M. Z., Hosain, N., Maruf, M. F., Chowdhury, M. A. Q., Hasan, N. K. M. M., Shawon, I. I., & Raqib, R. (2021). Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms. Scientific Reports, 11(1), 6263. https://doi.org/10.1038/s41598-021-85780-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pourabdollah, M., Javadi, M., Shamaei, A., Ziazi, M., Dorudinia, L., Seyedmehdi, A., & Karimi, S. (2014). Qualification study of two genomic DNA extraction methods in different clinical samples. Tanaffos, 13(4), 41–47.

    PubMed  PubMed Central  Google Scholar 

  28. Gado, A. M., Adam, A. N., & Aldahmash, B. A. (2013). Cardiotoxicity induced by cyclophosphamide in rats: Protective effect of curcumin. Journal of Research in Environmental Science and Toxicology, 2(4), 87–95.

    Google Scholar 

  29. Cawthon, R. M. (2002). Telomere measurement by quantitative PCR. Nucleic Acids Research, 30(10), e47. https://doi.org/10.1093/nar/30.10.e47

    Article  PubMed  PubMed Central  Google Scholar 

  30. Agahian, B., Lee, J. S., Nelson, J. H., & Johns, R. E. (1990). Arsenic levels in fingernails as a biological indicator of exposure to arsenic. American Industrial Hygiene Association Journal, 51(12), 646–651. https://doi.org/10.1080/15298669091370293

    Article  CAS  PubMed  Google Scholar 

  31. Cullen, W., & Reimer, K. J. (1989). Arsenic speciation in the environment. Chemical Reviews, 89, 713–764. https://doi.org/10.1021/cr00094a002

    Article  CAS  Google Scholar 

  32. Wilhelm, M., Pesch, B., Wittsiepe, J., Jakubis, P., Miskovic, P., Keegan, T., Nieuwenhuijsen, M. J., & Ranft, U. (2005). Comparison of arsenic levels in fingernails with urinary As species as biomarkers of arsenic exposure in residents living close to a coal-burning power plant in Prievidza District, Slovakia. Journal of Exposure Analysis and Environmental Epidemiology, 15(1), 89–98. https://doi.org/10.1038/sj.jea.7500350

    Article  CAS  PubMed  Google Scholar 

  33. Al-Forkan, M., Islam, S., Akter, R., Alam, S. S., Khaleda, L., Rahman, Z., & Chowdhury, D. (2016). A sub-chronic exposure study of arsenic on hematological parameters, liver enzyme activities, histological studies and accumulation pattern of arsenic in organs of wistar albino rats. Journal of Cytology & Histology. https://doi.org/10.4172/2157-7099.1000S5:006

    Article  Google Scholar 

  34. Rehman, K., Fatima, F., & Akash, M. S. H. (2019). Biochemical investigation of association of arsenic exposure with risk factors of diabetes mellitus in Pakistani population and its validation in animal model. Environmental Monitoring and Assessment. https://doi.org/10.1007/s10661-019-7670-2

    Article  PubMed  Google Scholar 

  35. Kumar, R., & Banerjee, T. K. (2016). Arsenic induced hematological and biochemical responses in nutritionally important catfish Clarias batrachus (L.). Toxicology Reports, 3, 148–152. https://doi.org/10.1016/j.toxrep.2016.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ola-Davies, O. E., & Akinrinde, A. S. (2016). Acute sodium Arsenite-induced hematological and biochemical changes in wistar rats: Protective effects of ethanol extract of Ageratum conyzoides. Pharmacognosy Research, 8, S26–S30. https://doi.org/10.4103/0974-8490.178645

    Article  PubMed  PubMed Central  Google Scholar 

  37. Douglas, D., Samaha, R. J., & Barnes, A. (1975). Arsenic intoxication as a cause of megaloblastic anemia. Blood, 45(2), 241–246.

    Article  Google Scholar 

  38. Hosen, S. M. I., Das, D., Kobi, R., Chowdhury, D. U. S., Alam, M. J., Rudra, B., Bakar, M. A., Islam, S., Rahman, Z., & Al-Forkan, M. (2016). Study of arsenic accumulation in rice and evaluation of protective effects of Chorchorus olitorius leaves against arsenic contaminated rice induced toxicities in Wistar albino rats. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-016-0091-8

    Article  PubMed  PubMed Central  Google Scholar 

  39. Balakumar, P., & Kaur, J. (2009). Arsenic exposure and cardiovascular disorders: An overview. Cardiovascular Toxicology, 9(4), 169–176. https://doi.org/10.1007/s12012-009-9050-6

    Article  CAS  PubMed  Google Scholar 

  40. Samani, N. J., Boultby, R., Butler, R., Thompson, J. R., & Goodall, A. H. (2001). Telomere shortening in atherosclerosis. Lancet (London, England), 358(9280), 472–473. https://doi.org/10.1016/S0140-6736(01)05633-1

    Article  CAS  PubMed  Google Scholar 

  41. Liu, L., Trimarchi, J. R., Navarro, P., Blasco, M. A., & Keefe, D. L. (2003). Oxidative stress contributes to arsenic-induced telomere attrition, chromosome instability, and apoptosis. Journal of Biological Chemistry, 278(34), 31998–32004. https://doi.org/10.1074/jbc.M303553200

    Article  CAS  PubMed  Google Scholar 

  42. Pusceddu, I., Kleber, M., Delgado, G., Herrmann, W., März, W., & Herrmann, M. (2018). Telomere length and mortality in the ludwigshafen risk and cardiovascular health study. PLoS One, 13(6), e0198373. https://doi.org/10.1371/journal.pone.0198373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hou, L., Zhu, Z. Z., Zhang, X., Nordio, F., Bonzini, M., Schwartz, J., Hoxha, M., Dioni, L., Marinelli, B., Pegoraro, V., Apostoli, P., Bertazzi, P. A., & Baccarelli, A. (2010). Airborne particulate matter and mitochondrial damage: A cross-sectional study. Environmental Health, 9(1), 48.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Liu, L. P., Cheng, K., Ning, M. A., Li, H. H., Wang, H. C., Li, F., Chen, S. Y., Qu, F. L., & Guo, W. Y. (2017). Association between peripheral blood cells mitochondrial DNA content and severity of coronary heart disease. Atherosclerosis, 261, 105–110. https://doi.org/10.1016/j.atherosclerosis.2017.02.013

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge the Cardiac Surgery Department and the Pathology Department of Chittagong Medical College and Hospital and the patients who enthusiastically participated in the research.

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This research was carried out by self-funding.

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Authors and Affiliations

  1. Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh

    Laila Khaleda, Syeda Kishuara Begum, Md. Abdur Rahman Apu, Rahee Hasan Chowdhury, Md. Jibran Alam, Amit Datta & Mohammad Al-Forkan

  2. Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

    Md. Zillur Rahman

  3. Department of Cardiac Surgery, Chittagong Medical College Hospital, Chittagong-4203, Bangladesh

    Nazmul Hosain

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  1. Laila Khaleda
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Contributions

LK: Conceptualization, Methodology, Supervision, Review & Editing; SKB: Investigation, data analysis, Visualization & Data curation, Writing manuscript,; MARA: Formal analysis, Visualization, Data curation & manuscript preparation; RHC: Review & Editing manuscript, MJ: Methodology, Writing & Editing; AD:Writing Visualization & Data Curation, ZR: Methodology, Investigation & Review, NH: Sample Collection, Methodology & Review; MAF: Conceptualization, Methodology, Review & Editing.

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Correspondence to Laila Khaleda.

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Ethical clearance was taken from the Ethical Review Board (ERB) of Chittagong Medical College and Hospital, Chittagong. Each family was informed about the study and written Informed consent was obtained under a protocol accredited by the ethical review committee of Chittagong Medical College and Hospital.

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Khaleda, L., Begum, S.K., Apu, M.A.R. et al. Arsenic-Induced Cardiovascular Diseases and their Correlation with Mitochondrial DNA Copy Number, Deletion, and Telomere Length in Bangladeshi Population. Cardiovasc Toxicol 24, 27–40 (2024). https://doi.org/10.1007/s12012-023-09812-7

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