EMERGING ROLES FOR INTERLEUKIN 11 IN VASCULAR DISEASES
Keywords:
interleukin 11, vascular diseases, small molecule drugsAbstract
Vascular diseases represent a leading global cause of morbidity and mortality, emphasizing the urgent need for effective therapeutic interventions. Interleukin-11 (IL-11), a member of the IL-6 cytokine family with established roles in autoimmune disease and tumor biology, has recently garnered interest due to its potential involvement in vascular pathology. Nevertheless, the precise biological functions and mechanistic actions of IL-11 in these conditions remain inadequately characterized. This review synthesizes current evidence on IL-11 expression, function, and signaling, and examines its roles across coronary artery disease, aortic disease, hypertension, cerebrovascular disease, and related vascular pathologies. Therefore, the development of small molecule inhibitors targeting IL-11 as a potential therapeutic target may offer new prospects in the treatment of vascular diseases.
References
1. Fallahtafti P, Soleimani H, Khanmohammadi S, et al. Global trends in cardiovascular mortality attributable to high body mass index: 1990-2021 analysis with future projections. Am J Prev Cardiol. 2025;24:101326. doi:10.1016/j.ajpc.2025.101326
2. Jia S, Liu Y, Yuan J. Evidence in guidelines for treatment of coronary artery disease. Adv Exp Med Biol. 2020;1177:37-73. doi:10.1007/978-981-15-2517-9_2
3. Schumacher D, Liehn EA, Nilcham P, et al. A neutralizing IL-11 antibody reduces vessel hyperplasia in a mouse carotid artery wire injury model. Sci Rep. 2021;11(1):20674. doi:10.1038/s41598-021-99880-y
4. Lokau J, Kespohl B, Kirschke S, Garbers C. The role of proteolysis in interleukin-11 signaling. Biochim Biophys Acta Mol Cell Res. 2022;1869(1):119135. doi:10.1016/j.bbamcr.2021.119135.
5. Lim WW, Dong J, Ng B, et al. Inhibition of IL11 signaling reduces aortic pathology in murine Marfan syndrome. Circ Res. 2022;130(5):728-740. doi:10.1161/circresaha.121.320381
6. Putoczki TL, Dobson RC, Griffin MD. The structure of human interleukin-11 reveals receptor-binding site features and structural differences from interleukin-6. Acta Crystallogr D Biol Crystallogr. 2014;70(9):2277-2285. doi:10.1107/S1399004714012267
7. Putoczki TL, Ernst M. IL-11 signaling as a therapeutic target for cancer. Immunotherapy. 2015;7(4):441-453. doi:10.2217/imt.15.17
8. Nguyen PM, Abdirahman SM, Putoczki TL. Emerging roles for interleukin-11 in disease. Growth Factors. 2019;37(1-2):1-11. doi:10.1080/08977194.2019.1620227.
9. Guo YT, Lu YY, Lu X, et al. Krüppel-like factor 15/interleukin 11 axis-mediated adventitial remodeling depends on extracellular signal-regulated kinases 1 and 2 activation in angiotensin II-induced hypertension. J Am Heart Assoc. 2021;10(16):e020554. doi:10.1161/jaha.120.020554.
10. Lindkvist M, Zegeye MM, Grenegård M, Ljungberg LU. Pleiotropic, unique and shared responses elicited by IL-6 family cytokines in human vascular endothelial cells. Int J Mol Sci. 2022;23(3):1448. doi:10.3390/ijms23031448.
11. Widjaja AA, Chothani S, Viswanathan S, et al. IL11 stimulates IL33 expression and proinflammatory fibroblast activation across tissues. Int J Mol Sci. 2022;23(16):8900. doi:10.3390/ijms23168900.
12. Gorabi AM, Kiaie N, Sahebkar A. The role of microRNAs in regulating cytokines and growth factors in coronary artery disease: the ins and outs. J Immunol Res. 2020;2020:5193036. doi:10.1155/2020/5193036
13. Tamura Y, Kohno H, Mohri T, et al. The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model. Ann Cardiothorac Surg. 2017;7(1):99-105. doi:10.21037/acs.2017.09.11
14. Kano HD, Sun W. Risk factors for aortic dissection. US Cardiol. 2023;17:e17. doi:10.15420/usc.2022.36
15. Xu Y, Ye J, Wang M, et al. Increased interleukin-11 levels in thoracic aorta and plasma from patients with acute thoracic aortic dissection. Clin Chim Acta. 2018;481:193-199. doi:10.1016/j.cca.2018.03.014.
16. Kurakula K, Smolders V, Tura-Ceide O, Goumans MJ. Endothelial dysfunction in pulmonary hypertension: cause or consequence? Biomedicines. 2021;9(1):57. doi:10.3390/biomedicines9010057.
17. Roger I, Milara J, Cortijo J. The role of JAK/STAT molecular pathway in vascular remodeling associated with pulmonary hypertension. Int J Mol Sci. 2021;22(9):4980. doi:10.3390/ijms22094980
18. Zhang B, Zhang HX, Shi ST, et al. Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury. Biomed Pharmacother. 2019;115:108816. doi:10.1016/j.biopha.2019.108816.
19. Yang W, Zhang S, Qi Z, et al. Interleukin-11 regulates the fate of adipose-derived mesenchymal stem cells via STAT3 signalling pathways. Cell Prolif. 2020;53(5):e12771. doi:10.1111/cpr.12771
20. Abu El-Asrar AM, Ahmad A, Gikandi PW, et al. Interleukin-11 overexpression and M2 macrophage density are associated with angiogenic activity in proliferative diabetic retinopathy. Ocul Immunol Inflamm. 2020;28(4):575-588. doi:10.1080/09273948.2019.1616772
21. Elshabrawy HA, Raemdonck KV, Shahara S, et al. IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells. Angiogenesis. 2018;21(2):215-228. doi:10.1007/s10456-017-9589-y
22. Wu J, Ma W, Qiu Z, Zhou Z. Roles and mechanism of IL-11 in vascular diseases. Front Cardiovasc Med. 2023;26(10):1171697. doi:10.3389/fcvm.2023.1171697.
23. Metcalfe RD, Hanssen E, Fung KY, et al. Structures of the interleukin 11 signalling complex reveal dynamics of gp130 extracellular domains and the inhibitory mechanism of a cytokine variant. Nat Commun. 2023;14:7543. doi:10.1038/s41467-023-42754-w.
24. Widjaja AA, Viswanathan S, et al. A neutralizing IL-11 antibody improves renal function and increases lifespan in a mouse model of Alport syndrome. J Am Soc Nephrol. 2022;33(4):718-730. doi:10.1681/asn.2021040577.
25. Osman EEA, Neamati N. Ironing out the mechanism of gp130 signaling. Pharmacol Rev. 2024;76(6):1399-1443. doi:10.1124/pharmrev.124.001245.
26. Lear S, Tafi R, Di Biasio VA, et al. De novo discovery of cyclic peptide inhibitors of IL-11 signaling. Bioorg Med Chem. 2025;119:118017. doi:10.1016/j.bmc.2024.118017.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 The authors
This work is licensed under a Creative Commons Attribution 4.0 International License.
