Endothelial factors and blood homocysteine level in adolescents with rheumatic diseases
DOI:
https://doi.org/10.14739/mmt.2024.1.298488Keywords:
rheumatic diseases, vascular endothelium function, homocysteine, vascular endothelial growth factor, brain natriuretic peptide, angiotensin-converting enzyme, adolescentsAbstract
It is known that the dysfunction of the endothelium has crucial role in many pathological conditions and underlines adverse cardiovascular events.
The aim of our study was to determine biologically active substances in the blood that affect endothelial function and homocysteine level in adolescents with rheumatic diseases.
Materials and methods. We examined 68 patients with rheumatic diseases, among them 25 patients with systemic lupus erythematosus (SLE) and 43 patients with juvenile idiopathic arthritis (JIA). Obtained results were compared with similar indicators of peers from the control group. All patients received basic therapy for 12 or more months at the time of examination. Biologically active substances (Homocysteine (Hcy), vascular endothelial growth factor (VEGF), high-sensitivity C-reactive protein (hs-CRP)) were studied by enzyme-linked immunosorbent assay, brain natriuretic peptide (NT-proBNP) by competitive immunoassay, and angiotensin-converting enzyme (ACE) by turbidimetric FAPGG kinetics method.
Results. Patients with rheumatic diseases had a significantly higher level of BNP (p < 0.01). These changes were most significant in patients with SLE. The level of Hcy did not differ from the similar indicator of the control group, but in patients with SLE it was significantly higher (p < 0.01) than in patients with JIA.
Conclusions. In patients with rheumatic diseases, biologically active substances level affecting the endothelium function depends on the disease. Biologically active substances affecting the function of the endothelium were within normal values. Thus, in children with SLE compared with JIA children, an increase in Hcy and NT-proBNP, and a decrease in ACE and hs-CRP protein were found. In children with JIA, normal levels of Hcy and ACE are accompanied by an increase in NT-proBNP and hs-CRP. In adolescents aged 10–18 years with SLE and JIA, multidirectional changes in biologically active substances and homocysteine, affecting the endothelial function of blood vessels were found.
References
Murdaca G, Colombo BM, Cagnati P, Gulli R, Spanò F, Puppo F. Endothelial dysfunction in rheumatic autoimmune diseases. Atherosclerosis. 2012;224(2):309-17. doi: https://doi.org/10.1016/j.atherosclerosis.2012.05.013
Tselios K, Gladman DD, Su J, Urowitz M. Impact of the new American College of Cardiology/American Heart Association definition of hypertension on atherosclerotic vascular events in systemic lupus erythematosus. Ann Rheum Dis. 2020;79(5):612-7. doi: https://doi.org/10.1136/annrheumdis-2019-216764
Katerenchuk IP, Tsyhanenko IV. Endotelialna dysfunktsiia ta kardiovaskuliarnyi ryzyk: prychyny, mekhanizmy rozvytku, klinichni proiavy, likuvannia i profilaktyka [Endothelial dysfunction and cardiovascular risk: causes, mechanisms of development, clinical manifestations, treatment and prevention]. Kyiv: Vydavnychyi dim Medknyha; 2017. Ukrainian.
Bordy R, Totoson P, Prati C, Marie C, Wendling D, Demougeot C. Microvascular endothelial dysfunction in rheumatoid arthritis. Nat Rev Rheumatol. 2018;14(7):404-20. doi: https://doi.org/10.1038/s41584-018-0022-8
Mauro D, Nerviani A. Endothelial Dysfunction in Systemic Lupus Erythematosus: Pathogenesis, Assessment and Therapeutic Opportunities. Rev Recent Clin Trials. 2018;13(3):192-8. doi: https://doi.org/10.2174/1574887113666180314091831
McMahon M, Seto R, Skaggs BJ. Cardiovascular disease in systemic lupus erythematosus. Rheumatol Immunol Res. 2021;2(3):157-72. doi: https://doi.org/10.2478/rir-2021-0022
Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Int J Mol Sci. 2021;22(8):3850. doi: https://doi.org/10.3390/ijms22083850
Kuriata OV, Sirenko OY. Kardiovaskuliarnyi ryzyk ta revmatolohichni zakhvoriuvannia (kardiorevmatolohichnyi syndrom) [Cardiovascular risk and rheumatological diseases (cardiorheumatological syndrome)]. Dnipro: Herda; 2017. Ukrainian.
Vynohradova OM, Minko LY, Slaba OM, Dyryk VT, Vykhtiuk TI, Batih VM. Homocysteine as a biomarker of vascular pathology. Ukrainskyi zhurnal medytsyny, biolohii ta sportu, 2023;8(41):14-20. doi: https://doi.org/10.26693/jmbs08.01.014
Ylä-Herttuala S, Rissanen TT, Vajanto I, Hartikainen J. Vascular Endothelial Growth Factors. J Am Coll Cardiol. March. 2007;49(10):1015-26. doi: https://doi.org/10.1016/j.jacc.2006.09.053
Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardiovasc Res. 2005;65(3):550-63. doi: https://doi/10.1016/j.cardiores.2004.12.002
Kumar A, Palfrey HA, Pathak R, Kadowitz PJ, Gettys TW, Murthy SN. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond). 2017;14:78. doi: https://doi/10.1186/s12986-017-0233-z
Gavrilenko TI, Ryzhkova NO, Parkhomenko OM, Dovgan NV. [Physiological significance of vascular endothelial growth factor in patients with acute forms of coronary artery disease]. Fiziologichnyi zhurnal. 2019;65(5):36-9. Ukrainian. doi: https://doi.org/10.15407/fz65.05.033
Smith GA, Fearnley GW, Tomlinson DC, Harrison MA, Ponnambalam S. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis. Biosci Rep. 2015;35(5):e00253. doi: https://doi.org/10.1042/BSR20150171
Fearnley GW, Smith GA, Abdul-Zani I, Yuldasheva N, Mughal NA, Homer-Vanniasinkam S, et al. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis. Biol Open. 2016;5(5):571-83. doi: https://doi.org/10.1242/bio.017434
Wong MKS. Angiotensin Converting Enzymes. Handbook of Hormones. 2016:263-65,e29D-1-e29D-4. doi: https://doi.org/10.1016/B978-0-12-801028-0.00254-3
Chen Y, Huang D, Yuan W, Chang J, Yuan Z, Wu D, et al. Lower Serum Angiotensin-Converting Enzyme Level in Relation to Hyperinflammation and Impaired Antiviral Immune Response Contributes to Progression of COVID-19 Infection. Infect Dis Ther. 2021;10(4):2431-46. doi: http://doi.org/10.1007/s40121-021-00513-8
Ghafouri-Fard S, Noroozi R, Omrani MD, Branicki W, Pośpiech E, Sayad A, et al. Angiotensin converting enzyme: A review on expression profile and its association with human disorders with special focus on SARS-CoV-2 infection. Vascul Pharmacol. 2020;130:106680. doi: https://doi.org/10.1016/j.vph.2020.106680
Vanderheyden M, Bartunek J, Goethals M. Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail. 2004;6(3):261-8. doi: https://doi.org/10.1016/j.ejheart.2004.01.004
Pandey KN. Molecular Signaling Mechanisms and Function of Natriuretic Peptide Receptor-A in the Pathophysiology of Cardiovascular Homeostasis. Front Physiol. 2021;12:693099. doi: https://doi.org/10.3389/fphys.2021.693099
Nakagawa H, Saito Y. Roles of Natriuretic Peptides and the Significance of Neprilysin in Cardiovascular Diseases. Biology (Basel). 2022;11(7):1017. doi: https://doi.org/10.3390/biology11071017
Little PJ, Askew CD, Xu S, Kamato D. Endothelial Dysfunction and Cardiovascular Disease: History and Analysis of the Clinical Utility of the Relationship. Biomedicines. 2021;9(6):699. doi: https://doi.org/10.3390/biomedicines9060699
Xu S, Ilyas I, Little PJ, Li H, Kamato D, Zheng X, et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies. Pharmacol Rev. 2021;73(3):924-67. doi: https://doi.org/10.1124/pharmrev.120.000096