Current Understanding of the Role of Adipokines in the Pathogenesis of Coronary Heart Disease

Introduction. The prevalence of abdominal obesity and its association with coronary artery disease are prerequisites for studying the relationships at the molecular level due to adipokines secreted by adipose tissue.

Purpose is to conduct a critical analysis of the data presented in available sources indexed in the databases of the Russian Science Citation Index and PubMed for the period mainly 2018–2026, devoted to the pathogenetic relationship of abdominal obesity and coronary heart disease through the effects of adipokines.

Results. A wide range (over 600) of adipokines can be differentiated depending on their involvement in atherogenesis as a key substrate of coronary heart disease into pro- and antiatherogenic and adipokines with an uncertain role. The role of antiatherogenic adipokines is realized by changing the lipid profile of plasma, anti-inflammatory, antioxidant properties. Adipokines with an uncertain role in atherogenesis are the object of close study and clarification of their role in the pathogenesis of coronary heart disease. The presented information expands the available information on the role of adipokines in the pathogenesis of coronary heart disease, and is a prerequisite for further research and improvement of diagnostic, prognostic, therapeutic, and preventive synergistic strategies in patients with coronary heart disease and abdominal obesity in clinical practice, including in the context of personalized biomolecular medicine aimed at reducing the global burden of atherosclerosis. 

1. Nowicka G. Obesity and obesity-related disorders-editorial. International Journal of Molecular Sciences. 2024;25(14):7954. DOI: https://doi.org/10.3390/ijms25147954.

2. Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: The linking mechanism and the complications. Archives of Medical Science. 2018;13(4):851–863. DOI: https://10.5114/aoms.2016.58928.

3. Dutheil F, Gordon BA, Naughton G, Crendal E, Courteix D, Chaplais E, et al. Cardiovascular risk of adipokines: A review. Journal of International Medical Research. 2018;46(6):2082–2095. DOI: https://10.1177/0300060517706578.

4. An SM, Cho SH, Yoon JC. Adipose tissue and metabolic health. Diabetes & Metabolism Journal. 2023;47(5):595–611. DOI: https://doi.org/10.4093/dmj.2023.0011.

5. Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: Inflammation, fibrosis, and impaired angiogenesis. Journal of Clinical Investigation. 2017;127:74–82. DOI: https://doi.org/10.1172/JCI88883.

6. Matar DB, Elahi MA, Sukkarieh H, Nassar WK, Aljada A. Unlocking the secrets: Adipose tissue dysfunction and atherosclerosis-mechanisms and innovative therapeutic approaches. Atherosclerosis. 2025;408:120424. DOI: https://doi.org/10.1016/j.atherosclerosis.2025.120424.

7. Jung HN, Jung CH. The role of anti-inflammatory adipokines in cardiometabolic disorders: Moving beyond adiponectin. International Journal of Molecular Sciences. 2021;22(24):13529. DOI: https://doi.org/10.3390/ijms222413529.

8. Liu L, Shi Z, Ji X, Zhang W, Luan J, Zahr T, et al. Adipokines, adiposity, and atherosclerosis. Cellular and Molecular Life Sciences. 2022;79(5):272. DOI: https://doi.org/10.1007/s00018-022-04286-2.

9. Raman P, Khanal S. Leptin in atherosclerosis: Focus on macrophages, endothelial and smooth muscle cells. International Journal of Molecular Sciences. 2021;22(11):5446. DOI: https://doi.org/10.3390/ijms22115446.

10. Minelli S, Minelli P, Montinari MR. Reflections on atherosclerosis: Lesson from the past and future research directions. Journal Multidisciplinary Healthcare. 2020;17:621–633. DOI: https://doi.org/10.2147/JMDH.S254016.

11. Kotlyarov S. Involvement of lipids and lipid mediators in inflammation and atherogenesis. Current Medicinal Chemistry. 2025;32(15):2971–2991. DOI: https://doi.org/10.2174/0109298673303369240312092913.

12. Savulescu-Fiedler I, Mihalcea R, Dragosloveanu S, Scheau C, Baz RO, Caruntu A, et al. The interplay between obesity and inflammation. Life. 2024;14(7):856. DOI: https://doi.org/10.3390/life14070856.

13. Engin AB. Message transmission between adipocyte and macrophage in obesity. Advances in Experimental Medicine and Biology. 2024;1460:273–295. DOI: https://doi.org/10.1007/978-3-031-63657-8_9.

14. Jia X, Lin H, Ding Y, Hu C, Wang S, Li M, et al. Phenotyping obesity through a two-dimensional tree structure reveals cardiometabolic heterogeneity. Cell Reports Medicine. 2025;6(11):102372. DOI: https://doi.org/10.1016/j.xcrm.2025.102372.

15. Koshelskaya OA, Narizhnaya NV, Kologrivova IV, Suslova TE, Kravchenko ES, Kharitonova OA, et al. Correlation of epicardial adipocytes hypertrophy with adipokines, inflammation and glucose and lipid metabolism. Siberian Journal of Clinical and Experimental Medicine. 2023;1(38):64–74. (In Russ.). DOI: https://doi.org/10.29001/2073-8552-2023-38-1-64-74.

16. McMillan R, Kirabo A. Chemerin as a mediator of hypertension and cardiometabolic diseases (a comprehensive review). Current Hypertension Reports. 2025;28(1):4. DOI: https://doi.org/10.1007/s11906-025-01354-3.

17. Favaretto F, Bettini S, Busetto L, Milan G, Vettor R. Adipogenic progenitors in different organs: Pathophysiological implications. Reviews in Endocrine & Metabolic Disorders. 2022;23(1):71–85. DOI: https://doi.org/10.1007/s11154-021-09686-6.

18. Xie L, Wang H, Hu J, Liu Z, Hu F. The role of novel adipokines and adipose-derived extracellular vesicles (ADEVs): Connections and interactions in liver diseases. Biochemical Pharmacology. 2024;222:116104. DOI: https://doi.org/10.1016/j.bcp.2024.116104.

19. Vilariño-García T, Polonio-González ML, Pérez-Pérez A, Ribalta J, Arrieta F, Aguilar M, et al. Role of leptin in obesity, cardiovascular disease, and type 2 diabetes. International Journal of Molecular Sciences. 2024;25(4):2338. DOI: https://doi.org/10.3390/ijms25042338.

20. Roy P, Kant R, Kaur A, Kumar H, Kumar R. Leptin resistance and cardiometabolic disorders: Bridging molecular pathways, genetic variants, and therapeutic innovation. Current Cardiology Reviews. 2025;21(5):e1573403X356019. DOI: https://doi.org/10.2174/011573403X356019250118170444.

21. Misch M, Puthanveetil P. The head-to-toe hormone: Leptin as an extensive modulator of physiologic systems. International Journal of Molecular Sciences. 2022;23(10):5439. DOI: https://doi.org/10.3390/ijms23105439.

22. Wang C, Chang L, Wang J, Xia L, Cao L, Wang W, et al. Leptin and risk factors for atherosclerosis: A review. Medicine (Baltimore). 2023;102(46):e36076. DOI: https://doi.org/10.1097/MD.0000000000036076.

23. Bruder A, Bruder-Nascimento T. Adipose tissue-derived adipokines in vascular physiology and pathophysiology: Insights and implications. Comprhensive Physiology. 2025;15(3):e70018. DOI: https://doi.org/10.1002/cph4.70018.

24. Odeberg J, Halling A, Ringborn M, Freitag M, Persson ML, Vaara I, et al. Markers of inflammation predicts long-term mortality in patients with acute coronary syndrome — a cohort study. BMC Cardiovascular Disorders. 2025;25 (1):190. DOI: https://doi.org/10.1186/s12872-025-04608-9.

25. Vasamsetti SB, Natarajan N, Sadaf S, Florentin J, Dutta P. Regulation of cardiovascular health and disease by visceral adipose tissue-derived metabolic hormones. The Journal of Physiology. 2023;601(11):2099–2120. DOI: https://doi.org/10.1113/JP282728.

26. Pan H, Lu X, Ye D, Feng Y, Wan J, Ye J. The molecular mechanism of thrombospondin family members in cardiovascular diseases. Frontiers in Cardiovascular Medicine. 2024;11:1337586. DOI: https://doi.org/10.3389/ fcvm.2024.1337586.

27. Liu B, Yang H, Song YS, Sorenson CM, Sheibani N. Thrombospondin-1 in vascular development, vascular function, and vascular disease. Seminars in Cell and Developmental Biology. 2024;155:32–44. DOI: https://doi.org/10.1016/j.semcdb.2023.07.011.

28. Galley JC, Singh S, Awata WMC, Alves JV, Bruder-Nascimento T. Adipokines: Deciphering the cardiovascular signature of adipose tissue. Biochemical Pharmacology. 2022;206:115324. DOI: https://doi.org/10.1016/j.bcp.2022.115324.

29. Del Cristo Rodríguez Pérez M, González DA, Rodríguez IM, Coello SD, Fernández FJC, Díaz BB, et al. Resistin as a risk factor for all-cause (and cardiovascular) death in the general population. Scientific Reports. 2022;12(1):19627. DOI: https://doi.org/10.1038/s41598-022-24039-2.

30. Musialik K, Miller-Kasprzak E, Walczak M, Markuszewski L, Bogdański P. The association between serum resistin level, resistin (-420C/G) single nucleotide variant, and markers of endothelial dysfunction, including salt taste preference in hypertensive patients. Nutrients. 2022;14(9):1789. DOI: https://doi.org/10.3390/nu14091789.

31. Yang HM, Kim J, Kim BK, Seo HJ, Kim JY, Lee JE, et al. Resistin regulates inflammation and insulin resistance in humans via the endocannabinoid system. Research. 2024;7:0326. DOI: https://doi.org/10.34133/research.0326.

32. Feijóo-Bandín S, Aragón-Herrera A, Moraña-Fernández S, Anido-Varela L, Tarazón E, Roselló-Lletí E, et al. Adipokines and inflammation: Focus on cardiovascular diseases. International Journal of Molecular Sciences. 2020;21(20):7711. DOI: https://doi.org/10.3390/ijms21207711.

33. Datta S, Koka S, Boini KM. Understanding the role of adipokines in cardiometabolic dysfunction: A review of current knowledge. Biomolecules. 2025;15(5):612. DOI: https://doi.org/10.3390/biom15050612.

34. Quispe R, Sweeney T, Martin SS, Jones SR, Allison MA, Budoff MJ, et al. Associations of adipokine levels with levels of remnant cholesterol: The multi-ethnic study of atherosclerosis. Journal of the American Heart Association. 2024;13(18):e030548. DOI: https://doi.org/10.1161/JAHA.123.030548.

35. Zhou L, Li JY, He PP, Yu XH, Tang CK. Resistin: Potential biomarker and therapeutic target in atherosclerosis. Clinica Chimica Acta. 2021;512:84–91. DOI: https://doi.org/10.1016/j.cca.2020.11.010.

36. Imiela AM, Stępnicki J, Zawadzka PS, Bursa A, Pruszczyk P. Chemerin as a driver of cardiovascular diseases: New perspectives and future directions. Biomedicines. 2025;13(6):1481. DOI: https://doi.org/10.3390/biomedicines13061481.

37. Pischon T, Nimptsch K. Blood-based obesity biomarkers and their relevance for disease risk. Nature Reviews Endocrinology. 2026;01:15. DOI: https://doi.org/10.1038/s41574-025-01229-2.

38. Wang B, Kou W, Ji S, Shen R, Ji H, Zhuang J, et al. Prognostic value of plasma adipokine chemerin in patients with coronary artery disease. Frontiers in Cardiovascular Medicine. 2022;9:968349. DOI: https://doi.org/10.3389/fcvm.2022.968349.

39. Kurihara O, Kim HO, Russo M, Araki M, Nakajima A, Lee H, et al. Relation of low-density lipoprotein cholesterol level to plaque rupture. The American Journal of Cardiology. 2020;134:48–54. DOI: https://doi.org/10.1016/j.amjcard.2020.08.016.

40. Mitsis A, Khattab E, Myrianthefs M, Tzikas S, Kadoglou NPE, Fragakis N, et al. Chemerin in the spotlight: Revealing its multifaceted role in acute myocardial infarction. Biomedicines. 2024;12(9):2133. DOI: https://doi.org/10.3390/biomedicines12092133.

41. Xie Y, Liu L. Role of Chemerin/ChemR23 axis as an emerging therapeutic perspective on obesity-related vascular dysfunction. Journal of Translational Medicine. 2022;20(1):141. DOI: https://doi.org/10.1186/s12967-021-03220-7.

42. Tang C, Chen G, Wu F, Cao Y, Yang F, You T, et al. Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes. Cardiovascular Research. 2023;119:1811–1824. DOI: https://doi.org/10.1093/cvr/cvad085.

43. Wabel EA, Krieger-Burke T, Watts SW. Vascular chemerin from PVAT contributes to norepinephrine and serotonin-induced vasoconstriction and vascular stiffness in a sex-dependent manner. American Journal of Physiology — Heart and Circulatory Physiology. 2024;327(6):H1577–H1589. DOI: https://doi.org/10.1152/ajpheart.00475.2024.

44. Ji Z-S, Jiang H, Xie Y, Wei QP, Yin XF, Ye JH, et al. Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization. Cell Biology and Toxicology. 2022;38(4):611–628. DOI: https://doi.org/10.1007/s10565-021-09636-7.

45. Yang HH, Wang X, Li S, Liu Y, Akbar R, Fan GC. Lipocalin family proteins and their diverse roles in cardiovascular disease. Pharmacology & Therapeutics. 2023;244:108385. DOI: https://doi.org/10.1016/j.pharmthera.2023.108385.

46. Lin TY, Leu HB, Wu YW, Tseng WK, Lin TH, Yeh HI, et al. Prognostic utility of neutrophil gelatinase-associated lipocalin (NGAL) levels for cardiovascular events in patients with stable coronary artery disease treated with percutaneous coronary intervention: A prospective longitudinal cohort study. Biomarker Research. 2025;13(1):24. DOI: https://doi.org/10.1186/s40364-025-00737-7.

47. Romejko K, Markowska M, Niemczyk S. The review of current knowledge on neutrophil gelatinase-associated lipocalin (NGAL). International Journal of Molecular Sciences. 2023;24(13):10470. DOI: https://doi.org/10.3390/ijms241310470.

48. Zhang H, Dhalla NS. The role of pro-inflammatory cytokines in the pathogenesis of cardiovascular disease. International Journal of Molecular Sciences. 2024;25(2):1082. DOI: https://doi.org/10.3390/ijms25021082.

49. Garlanda C, Di Ceglie I, Jaillon S. IL-1 family cytokines in inflammation and immunity. Cellular & Molecular Immunology. 2025;22(11):1345–1362. DOI: https://doi.org/10.1038/s41423-025-01358-8.

50. Garbuzova EV, Khudyakova AD, Alekseev S. E. Association of adipokines with coronary heart disease in young and middle-aged people. Atherosclerosis. 2023;19(4):444–456. (In Russ.). DOI: https://doi.org/10.52727/2078-256X-2023-19-2-444-456.

51. Zheng JB, Li XY, Zhu JM, Liu C, Song XT, Wang B, et al. Engineered immune-driven theranostics for clinical cardiology. Military Medical Research. 2025;12(1):76. DOI: https://doi.org/10.1186/s40779-025-00664-6.

52. González L, Rivera K, Andia ME, Martínez Rodriguez G. The IL-1 family and its role in atherosclerosis. International Journal of Molecular Sciences. 2022;24(1):17. DOI: http://doi.org/10.3390/ijms24010017.

53. Сhen S, Savas A, Atici A, Lee Y, Lane M, Aubuchon E, et al. Interleukin-1 signaling on vascular smooth muscle cells accelerates atherosclerosis in a murine model of Kawasaki disease. Journal of the American Heart Association. 2025;14(11):e040687. DOI: https://doi.org/10.1161/JAHA.124.040687.

54. Bolanle IO, de Liedekerke Beaufort GC, Weinberg PD. Transcytosis of LDL across arterial endothelium: Mechanisms and therapeutic targets. Arteriosclerosis, Thrombosis, and Vascular Biology. 2025;45(4):468–480. DOI: https://doi.org/10.1161/ATVBAHA.124.321549.

55. Chiorescu RM, Mocan M, Inceu AI, Buda AP, Blendea D, Vlaicu SI. Vulnerable atherosclerotic plaque: Is there a molecular signature? International Journal of Molecular Sciences. 2022;23(21):13638. DOI: https://doi.org/10.3390/ijms232113638.

56. Tall AR, Bornfeldt KE. Inflammasomes and atherosclerosis: A mixed picture. Circulation Research. 2023;132(11):1505–1520. DOI: https://doi.org/10.1161/CIRCRESAHA.123.321637.

57. Han W, Yang S, Xiao H, Wang M, Ye J, Cao L, et al. Role of adiponectin in cardiovascular diseases related to glucose and lipid metabolism disorders. International Journal of Molecular Sciences. 2022;23(24):15627. DOI: https://doi.org/10.3390/ijms232415627.

58. Aljafary MA, Al-Suhaimi EA. Adiponectin system (rescue hormone): The missing link between metabolic and cardiovascular diseases. Pharmaceutics. 2022;14(7):1430. DOI: https://doi.org/10.3390/pharmaceutics14071430.

59. Dikme R. Adiponectin paradox in coronary artery bypass graft patients: A comparative analysis of pericardial fluid and plasma levels. Cureus. 2025;17(10):e93766. DOI: https://doi.org/10.7759/cureus.93766.

60. Beberashvili I, Cohen-Cesla T, Khatib A, Hamad RA, Azar A, Stav K, et al. Comorbidity burden may explain adiponectin’s paradox as a marker of increased mortality risk in hemodialysis patients. Scientific Reports. 2021;11(1):9087. DOI: https://doi.org/10.1038/s41598-021-88558-0.

61. Tilg H, Ianiro G, Gasbarrini A, Adolph TE. Adipokines: Masterminds of metabolic inflammation. Nature Reviews Immunology. 2025;25(4):250–265. DOI: https://doi.org/10.1038/s41577-024-01103-8.

62. Zhou Y, Li H, Xia N. The interplay between adipose tissue and vasculature: Role of oxidative stress in obesity. Frontiers in Cardiovascular Medicine. 2021;8:650214. DOI: https://doi.org/10.3389/fcvm.2021.650214.

63. Zuo Y, Xiao T, Qiu X, Liu Z, Zhang S, Zhou N. Adiponectin reduces apoptosis of diabetic cardiomyocytes by regulating miR-711/TLR4 axis. Diabetology & Metabolic Syndrome. 2022;14(1):131. DOI: https://doi.org/10.1186/s13098-022-00904-y.

64. Huang G, Jian J, Liu CJ. Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances. Cytokine and Growth Factor Reviews. 2024;76:142–159. DOI: https://doi.org/10.1016/j.cytogfr.2023.11.001.

65. Qiao G, Lu Y, Wu J, Ren C, Lin R, Zhang C. Progranulin’s protective mechanisms and therapeutic potential in cardiovascular disease. Cells. 2025;14(11):762. DOI: https://doi.org/10.3390/cells14110762.

66. Nguyen AD, Nguyen TA, Singh RK, Eberle D, Zhang J, Abate JP, et al. Progranulin in the hematopoietic compartment protects mice from atherosclerosis. Atherosclerosis. 2018;277:145–154. DOI: https://doi.org/10.1016/j.atherosclerosis.2018.08.042.

67. Nádró B, Lőrincz H, Juhász L, Szentpéteri A, Sztanek F, Varga É, et al. Determination of serum progranulin in patients with untreated familial hypercholesterolemia. Biomedicines. 2022;10(4):771. DOI: https://doi.org/10.3390/biomedicines10040771.

68. Bruder-Nascimento A, Awata WMC, Alves JV, Singh S, Costa RM, Bruder-Nascimento T. Progranulin maintains blood pressure and vascular tone dependent on Ephrina2 and sortilin1 receptors and endothelial nitric oxide synthase activation. Journal of the American Heart Association. 2023;12(16):e030353. DOI: https://doi.org/10.1161/JAHA.123.030353.

69. Szczepańska E, Gietka-Czernel M. FGF21: A novel regulator of glucose and lipid metabolism and whole-body energy balance. Hormone and Metabolic Research. 2022;54(4):203–211. DOI: https://doi.org/10.1055/a-1778-4159.

70. Alyahya AM. The role of progranulin in ischemic heart disease and its related risk factors. European Journal of Pharmaceutical Sciences. 2022;175:106215. DOI: https://doi.org/10.1016/j.ejps.2022.106215.

71. Ohtsuki T, Satoh K, Shimizu T, Ikeda S, Kikuchi N, Satoh T, et al. Identification of adipsin as a novel prognostic biomarker in patients with coronary artery disease. Journal of the American Heart Association. 2019;8(23):e013716. DOI: https://doi.org/10.1161/JAHA.119.013716.

72. Hao S, Zhang J, Pei Y, Guo L, Liang Z. Complement factor D derived from epicardial adipose tissue participates in cardiomyocyte apoptosis after myocardial infarction by mediating PARP-1 activity. Cellular Signalling. 2023;101:110518. DOI: https://doi.org/10.1016/j.cellsig.2022.110518.

73. Man W, Song X, Xiong Z, Gu J, Lin J, Gu X, et al. Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by adipsin-regulated iron homeostasis. Frontiers in Cardiovascular Medicine. 2022;9:1003282. DOI: https://doi.org/10.3389/fcvm.2022.1003282.

74. Liu L, Chan M, Yu L, Wang W, Qiang L. Adipsin deficiency does not impact atherosclerosis development in Ldlr-/- mice. American Journal of Physiology — Endocrinology and Metabolism. 2021;320(1):E87–E92. DOI: https://doi.org/10.1152/ajpendo.00440.2020.

75. Laera N, Malerba P, Vacanti G, Nardin S, Pagnesi M, Nardin M. Impact of immunity on coronary artery disease: An updated pathogenic interplay and potential therapeutic strategies. Life. 2023;13(11):2128. DOI: https://doi.org/10.3390/life13112128.

76. Ali S, Alam R, Ahsan H, Khan S. Role of adipokines (omentin and visfatin) in coronary artery disease. Nutrition, Metabolism and Cardiovascular Diseases. 2023;33:483–493. DOI: https://doi.org/10.1016/j.numecd.2022.11.023.

77. Pedro WJS, Barbosa Júnior FV, Alves FNBR, Braga LV, Alves LR, Afonso JPR, et al. Role of adipokines chemerin, visfatin, and omentin in obesity and their inflammatory and metabolic implications. Biomedicines. 2025;13:2321. DOI: https://doi.org/10.3390/biomedicines13102321.

78. Farrag M, Ait Eldjoudi D, González-Rodríguez M, Cordero-Barreal A, Ruiz-Fernández C, Capuozzo M, et al. Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects. Frontiers in Endocrinology. 2023;13:1101091. DOI: https://doi.org/10.3389/fendo.2022.1101091.

79. Mazur-Bialy AI. Asprosin enhances cytokine production by a co-culture of fully differentiated mature adipocytes and macrophages leading to the exacerbation of the condition typical of obesity-related inflammation. International Journal of Molecular Sciences. 2023;24(6):5745. DOI: https://doi.org/10.3390/ijms24065745.

80. Lau WB, Ohashi K, Wang Y, Ogawa H, Murohara T, Ma XL, et al. Role of adipokines in cardiovascular disease. Circulation Journal. 2017;81(7):920–928. DOI: https://10.1253/circj.CJ-17-0458.