Uncovered mechanisms of cardioprotection in thyroid dysfunction

February 17, 2023
1211
Resume

Today, thyroid pathology affects more than 10% of the world’s adult population. In most patients with thyroid disease, there is a change in the concentration of thyroid hormones, which are involved in the regulation of the metabolism of almost all organs and systems. The cardiovascular system is very sensitive to fluctuations in the concentration of thyroid hormones, as evidenced by the increased prevalence of cardiac pathology and mortality in patients with thyroid dysfunction. The article presents various mechanisms by which thyroid hormones affect the cardiovascular system, describes the hemodynamic disturbances observed in hypo- and hyperthyroidism. It has been shown that timely treatment of even subclinical thyroid pathology and normalization of thyroid hormone levels has a potential benefit in preventing cardiovascular complications. The use of a combination of two biologically active substances — L-carnitine and L-arginine as an additional means of pathogenetic therapy of metabolic disorders associated with thyroid gland dysfunction is pathophysiologically justified.

References

  • 1. Chaker L., Razvi S., Bensenor I. et al. (2022) Hypothyroidism. Nat. Rev. Dis. Primers, 8(30). doi.org/10.1038/s41572-022-00357-7.
  • 2. Mooij C., Cheetham T., Verburg F. et al. (2022) European Thyroid Association Guideline for the management of pediatric Graves’ disease. Eur. Thyroid. J., 11(1): e210073.
  • 3. Paschou S., Bletsa E., Stampouloglou P. et al. (2022) Thyroid disorders and cardiovascular manifestations: an update. Endocrine, 75(3): 672–683. doi: 10.1007/s12020-022-02982-4.
  • 4. Stojković M., Žarković M. (2020) Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease. Cur. Pharmaceut. Design, 26(43): 5617–5627. doi.org/10.2174/1381612826666201118094747.
  • 5. Peppa M., Betsi G., Dimitriadis G. (2011) Lipid Abnormalities and Cardiometabolic Risk in Patients with Overt and Subclinical Thyroid Disease. J. Lipids, 2011: 575840. doi: 10.1155/2011/575840.
  • 6. Selmer C., Olesen J.B., Hansen M.L. et al. (2014) Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J. Clin. Endocrinol. Metab., 99(7): 2372–2382. doi: 10.1210/jc.2013-4184.
  • 7. Mastorci F., Sabatino L., Vassalle C., Pingitore A. (2020) Cardioprotection and Thyroid Hormones in the Clinical Setting of Heart Failure. Front. Endocrinol. (Lausanne), 10: 927. doi: 10.3389/fendo.2019.00927.
  • 8. Liu Y.Y., Brent G.A. (2010) Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends Endocrinol. Metab., 21(3): 166–173. dx.doi.org/10.1016/j.tem.2009.11.004.
  • 9. Gluvic Z.M., Obradovic M.M., Sudar-Milovanovic E.M. et al. (2020) Regulation of nitric oxide production in hypothyroidism. Biomed. Pharmacother., 124: 109881. doi: 10.1016/j.biopha.2020.109881.
  • 10. Guzmán-Gutiérrez E., Veas C., Leiva A. et al. (2014) Is a low level of free thyroxine in the maternal circulation associated with altered endothelial function in gestational diabetes? Front. Pharmacol., 5: 136. doi: 10.3389/fphar.2014.00136.
  • 11. Hernando V., Eliana M. (2015) Role of thyroid hormones in different aspects of cardiovascular system. Endocrinol. Metab. Synd., 4(2): 1000166. DOI: 10.4172/2161-1017.1000166.
  • 12. Zheng Y.S., Dong S.Y., Gong Y. et al. (2022) Comparison of Five Different Criteria for Diagnosis of Subclinical Hypothyroidism in a Large-Scale Chinese Population. Front. Endocrinol. (Lausanne), 13: 820414. doi: 10.3389/fendo.2022.820414.
  • 13. Jonklaas J. (2022) Optimal Thyroid Hormone Replacement. Endocr. Rev., 43(2): 366–404. doi: 10.1210/endrev/bnab031.
  • 14. Eom Y.S., Wilson J., Bernet V.J. (2022) Links between thyroid disorders and glucose homeostasis. Diabetes Metab. J., 46(2): 239–256. doi.org/10.4093/dmj.2022.0013.
  • 15. Jabbar A., Pingitore A., Pearce S. et al. (2017) Thyroid hormones and cardiovascular disease. Nat. Rev. Cardiol., 14(1): 39–55. doi: 10.1038/nrcardio.2016.174.
  • 16. Manolis A.A., Manolis T.A., Melita H., Manolis A.S. (2020) Subclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call? Trends Cardiovasc. Med., 30(2): 57–69. doi: 10.1016/j.tcm.2019.02.011.
  • 17. Tohidi M., Derakhshan A., Akbarpour S. et al. (2018) Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study. Horm. Metab. Res. 50(1): 37–43. doi: 10.1055/s-0043-121031.
  • 18. Yang G., Wang Y., Ma A., Wang T. (2019) Subclinical thyroid dysfunction is associated with adverse prognosis in heart failure patients with reduced ejection fraction. BMC Cardiovasc. Disord., 19(1): 83. doi: 10.1186/s12872-019-1055-x.
  • 19. Житникова Л.М. (2012) Метаболическая терапия, или кардиоцитопротекция — как необходимый компонент комбинированной терапии сердечно-сосудистых заболеваний. РМЖ (Русский медицинский журнал), 4: 137–143.
  • 20. Возможности метаболической терапии у пациентов с сердечно-сосудистой патологией (2018) Укр. мед. часопис, 2(1) (124): http://www.umj.com.ua/article/123917.
  • 21. Longo N., Frigeni M., Pasquali M. (2016) Carnitine transport and fatty acid oxidation. Biochim. Biophys. Acta, 1863(10): 2422–2435. doi: 10.1016/j.bbamcr.2016.01.023 330.
  • 22. Virmani M.A., Cirulli M. (2022) The Role of l-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Intern. J. Molec. Sci., 23(5): 2717. DOI: 10.3390/ijms23052717.
  • 23. Vaz F.M., Wanders R.J. (2002) Carnitine biosynthesis in mammals. Biochem. J., 361(Pt 3): 417–429. doi: 10.1042/0264-6021:3610417.
  • 24. Benvenga S., Amato A., Calvani M., Trimarchi F. (2004) Effects of carnitine on thyroid hormone action. Ann. N.Y. Acad. Sci., 1033: 158–167. doi: 10.1196/annals.1320.015.
  • 25. An J.H., Kim Y.J., Kim K.J. et al. (2016) L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial. Endocr. J., 63(10): 885–895.
  • 26. Sinclair C., Gilchrist J., Hennessey J., Kandula M. (2005) Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve, 32: 357–359. doi: 10.1002/mus.20336.
  • 27. De Felice S., Gilgore S. (1966) The antagonistic effect of carnitine in hyperthyroidism. Preliminary report. J. N. Drugs, 6: 351–353. doi: 10.1177/009127006600600607.
  • 28. Benvenga S., Lakshmanan M., Trimarchi F. (2000) Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake. Thyroid, 12: 1043–1050. doi: 10.1089/thy.2000.10.1043.
  • 29. Chee R., Agah R., Vita R., Benvenga S. (2014) Severe hyperthyroidism treated with L-carnitine, propranolol, and finally with thyroidectomy in a seriously ill cancer patient. Hormones, 13: 407–412.
  • 30. Nordio M. (2017) A novel treatment for subclinical hyperthyroidism: A pilot study on the beneficial effects of L-carnitine and selenium. Eur. Rev. Med. Pharmacol. Sci., 21: 2268–2273.
  • 31. Benvenga S., Ruggeri R., Russo A. et al. (2001) Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: A randomized, double-blind, placebo-controlled clinical trial. J. Clin. Endocrinol. Metab., 86: 3579–3594. doi: 10.1210/jcem.86.8.7747.
  • 32. Wang Z.Y., Liu Y.Y., Liu G.H. et al. (2018) l-Carnitine and heart disease. Life Sci., 194: 88–97. doi: 10.1016/j.lfs.2017.12.015.
  • 33. Xue Y.Z., Wang L.X., Liu H.Z. et al. (2007) L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction. Cardiovasc. Drugs Ther., 21: 445–448. doi: 10.1007/s10557-007-6056-9.
  • 34. Singh R.B., Niaz M.A., Agarwal P. et al. (1996) A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction. Postgrad. Med. J., 72: 45–50. doi: 10.1136/pgmj.72.843.45.
  • 35. Askarpour M., Hadi A., Symonds M.E., Miraghajani M. (2019) Efficacy of L-carnitine supplementation for management of blood lipids: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Nutrition, metabolism, and cardiovascular diseases, 29(11). DOI: 10.1016/j.numecd.2019.07.012.
  • 36. Гонський Я.І., Максимчук Т.П. (2001) Біохімія людини. Укрмедкнига, Тернопіль, 736 с.
  • 37. Banjarnahor S., Rodionov R.N., König J., Maas R. (2020) Transport of L-Arginine Related Cardiovascular Risk Markers. J. Clin. Med., 9(12): 3975. doi: 10.3390/jcm9123975.
  • 38. Toral M., Jimenez R., Montoro-Molina S. et al. (2018) Thyroid hormones stimulate L-arginine transport in human endothelial cells. J. Endocrinol., 239(1): 49–62. doi.org/10.1530/JOE-18-0229.
  • 39. Bronte V., Serafini P., Mazzoni A. et al. (2003) L-аrginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol., 24: 302–306.
  • 40. Verma M., Dahiya K., Ghalaut V. et al. (2015) Thyroid disorders and nitric oxide levels. J. Science, 5(1): 4–8.
  • 41. Huseyin V., Tamer M., Weiskirchen R. (2021) Evaluation of Arginine-Nitric Oxide Pathway in Patients with Hyperthyroidism. Electronic J. General Med., 18(2): em278. DOI: 10.29333/ejgm/9696.