Ukr.Biochem.J. 2026; Volume 98, Issue 1, Jan-Feb, pp. 49-57

doi: https://doi.org/10.15407/ubj98.01.049

Interplay of sclerostin and cytokines of interleukin-6 family in the pathophysiology of coronary artery disease

11.02.2026   Uncategorized

S. S. Rozoqi1, T. A. Allwsh2*

1Department of Medical Laboratory Technology,
Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil, Iraq;
2Department of Chemistry, Collage of Science, University of Mosul, Mosul, Iraq
*e-mail: thekraaliallwsh@uomosul.edu.iq

Received: 09 June 2025; Revised: 25 September 2025;
Accepted: 30 January 2026; Available on-line: 23 February 2026

Sclerostin, a Wnt/β-catenin signaling antagonist, plays a predominant role in bone metabolism and is also expressed in cardiovascular tissues. The level of this glycoprotein is associated with aortic stiffness and vascular calcification in coronary artery disease (CAD). Our study explored the relationship between the levels of sclerostin, cytokines of interleukin-6 family and prostaglandin E2 (PGE2) in the blood serum of CAD patients. The study included two groups of patients : 80 patients aged 46-74 with a stable coronary heart disease, and 80 patients aged 46-70 as a control group. The levels of oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1) and prostaglandin E2 (PGE2) were estimated with ELISA. The result have shown a highly significant decrease of sclerostin in conjunction with the increase of OSM, CT-1, LIF levels and along with the decrease of PGE2 level in the serum of patient with CAD comparing with control group. Pearson correlation analysis showed a significant relationship between sclerostin and OSM, CT-1, LIF, PGE2 concentrations. ROC curve analysis indicated that patients at risk for coronary heart disease could be identified with a specificity of 0.975 when their serum sclerostin level was greater than 88.325 pg/ml. Therefore, sclerostin could play a critical role in CAD and may be useful for monitoring disease progression.

Keywords: , , , , ,

References:

  1. Shaya GE, Leucker TM, Jones SR, Martin SS, Toth PP. Coronary heart disease risk: Low-density lipoprotein and beyond. Trends Cardiovasc Med. 2022;32(4):181-194. PubMed, CrossRef
  2. Thikra Ali Allwsh, Noori Mohammed Aziz. Clinical study of copeptin in serum patients of heart diseases. Tikrit J Pure Sci. 2023;20(3):99-107. CrossRef
  3. Golledge J, Thanigaimani S. Role of Sclerostin in Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2022;42(7):e187-e202. PubMed, CrossRef
  4. Chiu SH, Wu WT, Yao TK, Peng CH, Yeh KT. Sclerostin and Cardiovascular Risk: Evaluating the Cardiovascular Safety of Romosozumab in Osteoporosis Treatment. Biomedicines. 2024;12(12):2880.
    PubMed, PubMedCentral, CrossRef
  5. Kubin T, Gajawada P, Bramlage P, Hein S, Berge B, Cetinkaya A, Burger H, Schönburg M, Schaper W, Choi YH, Richter M. The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure. Int J Mol Sci. 2022;23(3):1811. PubMed, PubMedCentral, CrossRef
  6. Rezaeeyan H, Moghimian-Boroujeni B, Abdolalian M, Javan M. The Role of Leukemia Inhibitory Factor in Cardiovascular Disease: Signaling in Inflammation, Coagulation, and Angiogenesis. J Tehran Heart Cent. 2024;19(1):6-13. PubMed, PubMedCentral, CrossRef
  7. Schanstra JP, Luong TT, Makridakis M, Van Linthout S, Lygirou V, Latosinska A, Alesutan I, Boehme B, Schelski N, Von Lewinski D, Mullen W, Nicklin S, Delles C, Feuillet G, Denis C, Lang F, Pieske B, Bascands JL, Mischak H, Saulnier-Blache JS, Voelkl J, Vlahou A, Klein J. Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment. JCI Insight. 2019;4(10):e125638. PubMed, PubMedCentral, CrossRef
  8. Jougasaki M. Cardiotrophin-1 in cardiovascular regulation. Adv Clin Chem. 2010;52:41-76. PubMed, CrossRef
  9. Xiao CY, Yuhki K, Hara A, Fujino T, Kuriyama S, Yamada T, Takayama K, Takahata O, Karibe H, Taniguchi T, Narumiya S, Ushikubi F. Prostaglandin E2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP4. Circulation. 2004;109(20):2462-2468. PubMed, CrossRef
  10. Tobias JH. Sclerostin and Cardiovascular Disease. Curr Osteoporos Rep. 2023;21(5):519-526. PubMed, PubMedCentral, CrossRef
  11. Wolf CL, Pruett C, Lighter D, Jorcyk CL. The clinical relevance of OSM in inflammatory diseases: a comprehensive review. Front Immunol. 2023;14:1239732. PubMed, PubMedCentral, CrossRef
  12. Wang J, Chang CY, Yang X, Zhou F, Liu J, Feng Z, Hu W. Leukemia inhibitory factor, a double-edged sword with therapeutic implications in human diseases. Mol Ther. 2023;31(2):331-343. PubMed, PubMedCentral, CrossRef
  13. Villacorta H. Cardiotrophin-1 in Patients with Acute Coronary Syndromes: Does it Have a Role? Int J Cardiovasc Sci. 2021;34(5 Supl 1):22-23. CrossRef
  14. Gomez I, Foudi N, Longrois D, Norel X. The role of prostaglandin E2 in human vascular inflammation. Prostaglandins Leukot Essent Fatty Acids. 2013;89(2-3):55-63. PubMed, CrossRef
  15. Tuck MK, Chan DW, Chia D, Godwin AK, Grizzle WE, Krueger KE, Rom W, Sanda M, Sorbara L, Stass S, Wang W, Brenner DE. Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2009;8(1):113-117. PubMed, PubMedCentral, CrossRef
  16.  Keys A, Fidanza F, Karvonen MJ, Kimura N, Taylor HL. Indices of relative weight and obesity. J Chronic Dis. 1972;25(6):329-343. PubMed, CrossRef
  17. Mohammed ZH, Allwsh TA. Nesfatin-1: Relation to oxidative stress and inflammation markers for newly diagnosed myocardial infarction patients in Mosul/Iraq. J Med Pharm Chem Res. 2025;7(4):570-580. CrossRef
  18. De Jongh FW, Pouwels S, De Jongh MC, Dubois EA, van Schaik RHN. The Predictive Power of the 14-51 Ng/L High Sensitive Troponin T (hsTnT) Values for Predicting Cardiac Revascularization in a Clinical Setting. J Clin Med. 2022;11(23):7147. PubMed, PubMedCentral, CrossRef
  19. Milovanova LY, Dobrosmyslov IA, Milovanov YS, Taranova MV, Kozlov VV, Milovanova SY, Kozevnikova EI. Fibroblast growth factor-23 (FGF-23) / soluble Klotho protein (sKlotho) / sclerostin glycoprotein ratio disturbance is a novel risk factor for cardiovascular complications in ESRD patients receiving treatment with regular hemodialysis or hemodiafiltration. Ter Arkh. 2018;90(6):48-54. PubMed, CrossRef
  20. He W, Li C, Chen Q, Xiang T, Wang P, Pang J. Serum sclerostin and adverse outcomes in elderly patients with stable coronary artery disease undergoing percutaneous coronary intervention. Aging Clin Exp Res. 2020;32(10):2065-2072. PubMed, PubMedCentral, CrossRef
  21. Zheng S, Wei J, Chen P, Chen F, Yang G. Sclerostin aggravates cardiac remodeling after myocardial infarction by inhibition of Wnt/β-catenin signaling pathway. J Thorac Dis. 2022;14(5):1563-1577. PubMed, PubMedCentral, CrossRef
  22. González-Salvatierra S, García-Fontana C, Lacal J, Andújar-Vera F, Martínez-Heredia L, Sanabria-de la Torre R, Ferrer-Millán M, Moratalla-Aranda E, Muñoz-Torres M, García-Fontana B. Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells. Cardiovasc Diabetol. 2023;22(1):301. PubMed, PubMedCentral, CrossRef
  23. Jasim RF, Allwsh TA. Orexin a hormone and its relation to coronary heart diseases. Res J Pharm Technol. 2021;14(3):1417-1422. CrossRef
  24. Novo-Rodríguez C, García-Fontana B, Luna-Del Castillo JD, Andújar-Vera F, Ávila-Rubio V, García-Fontana C, Morales-Santana S, Rozas-Moreno P, Muñoz-Torres M. Circulating levels of sclerostin are associated with cardiovascular mortality. PLoS One. 2018;13(6):e0199504. PubMed, PubMedCentral, CrossRef
  25. Ikeda S, Sato K, Takeda M, Miki K, Aizawa K, Takada T, Fukuda K, Shiba N. Oncostatin M is a novel biomarker for coronary artery disease – A possibility as a screening tool of silent myocardial ischemia for diabetes mellitus. Int J Cardiol Heart Vasc. 2021;35:100829. PubMed, PubMedCentral, CrossRef
  26. Ikeda S, Sato K, Takeda M, Shinozaki M, Miki K, Hirano M, Fukuda K, Shiba N. Oncostatin M mediates cardioprotection via angiogenesis in ischemic heart disease. Am Heart J Plus. 2023;35:100331. PubMed, PubMedCentral, CrossRef
  27. Albasanz-Puig A, Murray J, Preusch M, Coan D, Namekata M, Patel Y, Dong ZM, Rosenfeld ME, Wijelath ES. Oncostatin M is expressed in atherosclerotic lesions: a role for Oncostatin M in the pathogenesis of atherosclerosis. Atherosclerosis. 2011;216(2):292-298. PubMed, CrossRef
  28. Stawski L, Trojanowska M. Oncostatin M and its role in fibrosis. Connect Tissue Res. 2019;60(1):40-49. PubMed, PubMedCentral, CrossRef
  29. Liu C, Wu J, Jia H, Lu C, Liu J, Li Y, Guo M. Oncostatin M promotes the ox-LDL-induced activation of NLRP3 inflammasomes via the NF-κB pathway in THP-1 macrophages and promotes the progression of atherosclerosis. Ann Transl Med. 2022;10(8):456. PubMed, PubMedCentral, CrossRef
  30. Calabrò P, Limongelli G, Riegler L, Maddaloni V, Palmieri R, Golia E, Roselli T, Masarone D, Pacileo G, Golino P, Calabrò R. Novel insights into the role of cardiotrophin-1 in cardiovascular diseases. J Mol Cell Cardiol. 2009;46(2):142-148. PubMed, CrossRef
  31. Konii H, Sato K, Kikuchi S, Okiyama H, Watanabe R, Hasegawa A, Yamamoto K, Itoh F, Hirano T, Watanabe T. Stimulatory effects of cardiotrophin 1 on atherosclerosis. Hypertension. 2013;62(5):942-950. PubMed, CrossRef
  32. Miteva K, Baptista D, Montecucco F, Asrih M, Burger F, Roth A, Fraga-Silva RA, Stergiopulos N, Mach F, Brandt KJ. Cardiotrophin-1 Deficiency Abrogates Atherosclerosis Progression. Sci Rep. 2020;10(1):5791. PubMed, PubMedCentral, CrossRef
  33. Rolfe BE, Stamatiou S, World CJ, Brown L, Thomas AC, Bingley JA, Worth NF, Campbell JH. Leukaemia inhibitory factor retards the progression of atherosclerosis. Cardiovasc Res. 2003;58(1):222-230. PubMed, CrossRef
  34. Guo X, Ma L. Inflammation in coronary artery disease-clinical implications of novel HDL-cholesterol-related inflammatory parameters as predictors. Coron Artery Dis. 2023;34(1):66-77. PubMed, PubMedCentral, CrossRef
  35. Gao S, Li D, Wang B, Zhang H, Chen L. Two promising approaches in the treatment of myocardial infarction: stem cells and gene therapy. Front Cardiovasc Med. 2025;12:1540066. PubMed, PubMedCentral, CrossRef
  36. Kodama H, Fukuda K, Pan J, Makino S, Baba A, Hori S, Ogawa S. Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, activates the JAK/STAT pathway in rat cardiomyocytes. Circ Res. 1997;81(5):656-663. PubMed, CrossRef
  37. Meisel SR, Shimon I, Edgington TS, Melmed S, Cercek B, Shah PK. Leukaemia inhibitory factor enhances tissue factor expression in human monocyte-derived macrophages: a gp130-mediated mechanism. Br J Haematol. 1999;107(4):747-755. PubMed, CrossRef
  38. Mackman N. The role of tissue factor and factor VIIa in hemostasis. Anesth Analg. 2009;108(5):1447-1452. PubMed, PubMedCentral, CrossRef
  39. Iwamoto R, Koide M, Udagawa N, Kobayashi Y. Positive and Negative Regulators of Sclerostin Expression. Int J Mol Sci. 2022;23(9):4895. PubMed, PubMedCentral, CrossRef
  40. Suzuki J, Ogawa M, Watanabe R, Takayama K, Hirata Y, Nagai R, Isobe M. Roles of prostaglandin E2 in cardiovascular diseases. Int Heart J. 2011;52(5):266-269. PubMed, CrossRef
  41. Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. J Lipid Res. 2009;50(Suppl):S29-S34.PubMed, PubMedCentral, CrossRef
  42. Kakutani Y, Shioi A, Shoji T, Okazaki H, Koyama H, Emoto M, Inaba M. Oncostatin M Promotes Osteoblastic Differentiation of Human Vascular Smooth Muscle Cells Through JAK3-STAT3 Pathway. J Cell Biochem. 2015;116(7):1325-1333. PubMed, CrossRef
  43. Sun H, Wang Y. Prostaglandin E2 in remote control of myocardial remodeling. Circulation. 2012;125(23):2818-2820. PubMed, PubMedCentral, CrossRef
  44. Kocełak P, Puzianowska-Kuźnicka M, Olszanecka-Glinianowicz M, Chudek J. Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification. Adv Clin Exp Med. 2024;33(5):519-532. PubMed, CrossRef
  45. Malaval L, Liu F, Vernallis AB, Aubin JE. GP130/OSMR is the only LIF/IL-6 family receptor complex to promote osteoblast differentiation of calvaria progenitors. J Cell Physiol. 2005;204(2):585-593. PubMed, CrossRef
  46. Weivoda MM, Chew CK, Monroe DG, Farr JN, Atkinson EJ, Geske JR, Eckhardt B, Thicke B, Ruan M, Tweed AJ, McCready LK, Rizza RA, Matveyenko A, Kassem M, Andersen TL, Vella A, Drake MT, Clarke BL, Oursler MJ, Khosla S. Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism. Nat Commun. 2020;11(1):87. PubMed, PubMedCentral, CrossRef
  47. Catalano A, Bellone F, Morabito N, Corica F. Sclerostin and Vascular Pathophysiology. Int J Mol Sci. 2020;21(13):4779. PubMed, PubMedCentral, CrossRef
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