Interleukin-11 and cardiovascular pathology

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Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. An important task in cardiology is the search and study of new biomarkers. Scientific interest is actively focused on the study of interleukin-11 (IL-11).

The purpose of the literature review was to analyze experimental and clinical studies devoted to the study of IL-11 as a diagnostic and prognostic marker in CVD.

Material and methods. The article provides an overview of current publications. An analysis of literature sources was carried out, including all relevant publications in the databases PubMed, RSCI, MedLine, Google Scholar, Science Direct.

Results. In endothelial cells, IL-11 primarily promotes angiogenesis, thereby exerting a beneficial effect on coronary heart disease. IL-11 also promotes vascular remodeling by inducing smooth muscle cell transformation and fibroblast activation. IL-11 may be involved in the onset and progression of pulmonary hypertension through the JAK/STAT3 pathway and aortic dissection processes through the non-classical ERK pathway.

Conclusion. The presented literature review indicates the potentially important diagnostic and prognostic value of IL-11 assessment. Regulating the concentration and expression of IL-11 may be a promising strategy for the treatment of CVD.

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About the authors

Amina M. Alieva

Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health of Russia

Author for correspondence.
Email: amisha_alieva@mail.ru
ORCID iD: 0000-0001-5416-8579

Associate Professor, Department of Hospital Therapy named after Academician G.I. Storozhakov, Faculty of Medicine

Russian Federation, Moscow

Igor G. Nikitin

Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health of Russia

Email: igor.nikitin.64@mail.ru
ORCID iD: 0000-0003-1699-0881

Head of the Department of Hospital Therapy named after Academician G.I. Storozhakov, Faculty of Medicine, Doctor of Medical Sciences, Professor

Russian Federation, Moscow

Ramiz K. Valiev

Moscow Clinical Research Center named after A.S. Loginov of the Department of Health of Moscow

Email: radiosurgery@bk.ru
ORCID iD: 0000-0003-1613-3716

Head of Oncosurgical Department, Candidate of Medical Sciences

Russian Federation, Moscow

Irina E. Baykova

Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health of Russia

Email: 1498553@mail.ru
ORCID iD: 0000-0003-0886-6290

Associate Professor, Department of Hospital Therapy, Academician G.I. Storozhakov Medical Faculty, Candidate of Medical Sciences

Russian Federation, Moscow

Irina A. Kotikova

Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health of Russia

Email: kotikova.ia@mail.ru
ORCID iD: 0000-0001-5352-8499

student of the Faculty of Medicine

Russian Federation, Moscow

References

  1. Gaidai O., Cao Y., Loginov S. Global Cardiovascular Diseases Death Rate Prediction. Curr. Probl. Cardiol. 2023; 48 (5): 101622. doi: 10.1016/j.cpcardiol.2023.101622.
  2. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021; 398 (10304): 957–80. doi: 10.1016/S0140-6736(21)01330-1.
  3. 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.
  4. Алиева А.М., Алмазова И.И., Пинчук Т.В., Резник Е.В., Федулаев Ю.Н., Никитин И.Г. Значение копептина в диагностике и прогнозе течения сердечно-сосудистых заболеваний. Клиническая медицина. 2020; 98 (3): 203–9. doi: 10.30629/0023-2149-2020-98-3-203-209. [Aliyevа A.M., Almazova I.I., Pinchuk T.V., Resnick E.V., Fedulaev Yu.N., Nikitin I.G. The value of copeptin in the diagnosis and prognosis of cardiovascular diseases. Clinical Medicine (Russian Journal). 2020; 98 (3): 203–9. doi: 10.30629/0023-2149-2020-98-3-203-209 (in Russian)]
  5. Голухова Е.З., Теряева Н.Б., Алиева А.М. Натрийуретические пептиды – маркеры и факторы прогноза при хронической сердечной недостаточности. Креативная кардиология. 2007; 1–2: 126–36. [Goluhova E.Z., Teryaeva N.B., Alieva A.M. Natrijureticheskie peptidy – markery i faktory prognoza pri hronicheskoj serdechnoj nedostatochnosti. Kreativnaya kardiologiya. 2007; 1–2: 126–36 (in Russian)]
  6. Голухова Е.З., Алиева А.М. Клиническое значение определения натрийуретических пептидов у больных с хронической сердечной недостаточностью. Кардиология и сердечно-сосудистая хирургия. 2007; 47 (1): 45–51. [Goluhova E.Z., Alieva A.M. Klinicheskoe znachenie opredeleniya natrijureticheskih peptidov u bol’nyh s hronicheskoj serdechnoj nedostatochnost’yu. Kardiologiya i serdechno-sosudistaya hirurgiya. 2007; 47 (1): 45–51 (in Russian)]
  7. Алиева А.М., Пинчук Т.В., Воронкова К.В., Шнахова Л.М., Эттингер О.А., Ахмедова М.Ф., Валиев Р.К., Калова М.Р., Гасанова Э.Т., Никитин И.Г. Неоптерин – биомаркер хронической сердечной недостаточности (обзор современной литературы). Consilium Medicum. 2021; 23 (10): 756–9. doi: 10.26442/20751753.2021.10.201113. [Alieva A.M., Pinchuk T.V., Voronkova K.V., Shnakhova L.M., Ettinger O.A., Akhmedova M.F., Valiev R.K., Kalova M.R., Hasanova E.T., Nikitin I.G. Neopterin is a biomarker of chronic heart failure (review of modern literature). Consilium Medicum. 2021; 23 (10): 756–9. doi: 10.26442/20751753.2021.10.201113. (in Russian)]
  8. Maroni P., Bendinelli P., Ferraretto A., Lombardi G. Interleukin 11 (IL-11): Role(s) in Breast Cancer Bone Metastases. Biomedicines. 2021; 9 (6): 659. doi: 10.3390/biomedicines9060659.
  9. Wu J., Ma W., Qiu Z., Zhou Z. Roles and mechanism of IL-11 in vascular diseases. Front. Cardiovasc. Med. 2023; 10: 1171697. doi: 10.3389/fcvm.2023.1171697.
  10. Haybar H., Bandar B., Torfi E., Mohebbi A., Saki N. Cytokines and their role in cardiovascular diseases. Cytokine. 2023; 169: 156261. doi: 10.1016/j.cyto.2023.156261.
  11. Mishra K.P., Bakshi J., Sharma G., Singh S., Panjwani U. A Comparative Analysis of Effectiveness of Recombinant Interleukin-11 Versus Papaya Leaf Extract for Treatment of Thrombocytopenia: A Review. Indian J. Clin. Biochem. 2023; 38 (3): 297–304. doi: 10.1007/s12291-022-01097-x.
  12. Nguyen P.M., Abdirahman S.M., Putoczki T.L. Emerging roles for Interleukin-11 in disease. Growth Factors. 2019; 37 (1–2): 1–11. doi: 10.1080/08977194.2019.1620227.
  13. Corden B., Adami E., Sweeney M., Schafer S., Cook S.A. IL-11 in cardiac and renal fibrosis: Late to the party but a central player. Br. J. Pharmacol. 2020; 177 (8): 1695–708. doi: 10.1111/bph.15013.
  14. Cook S.A., Schafer S. Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation. Annu Rev. Med. 2020; 71: 263–76. doi: 10.1146/annurev-med-041818-011649.
  15. Zhang X., Wu H., Dobson J.R., Browne G., Hong D., Akech J., Languino L.R., Stein G.S., Lian J.B. Expression of the IL-11 Gene in Metastatic Cells Is Supported by Runx2-Smad and Runx2-cJun Complexes Induced by TGFβ1. J. Cell. Biochem. 2015; 116: 2098–108. doi: 10.1002/jcb.25167.
  16. Bamba S., Andoh A., Yasui H., Makino J., Kim S., Fujiyama Y. Regulation of IL-11 expression in intestinal myofibroblasts: Role of c-Jun AP-1- and MAPK-dependent pathways. Am. J. Physiol. Gastrointest. Liver Physiol. 2003; 285: G529–38. doi: 10.1152/ajpgi.00050.2003.
  17. Gustafsson K.L.R., Renné T., Söderberg-Naucler C., Butler L.M. Human cytomegalovirus replication induces endothelial cell interleukin-11. Cytokine. 2018; 111: 563–6. doi: 10.1016/j.cyto.2018.05.018.
  18. Ng B., Cook S.A., Schafer S. Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway. Exp. Mol. Med. 2020; 52 (12): 1871–8. doi: 10.1038/s12276-020-00531-5.
  19. Gerritsen M.E., Tomlinson J.E., Zlot C., Ziman M., Hwang S. Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells. Br. J. Pharmacol. 2003; 140 (4): 595–610. doi: 10.1038/sj.bjp.0705494.
  20. Mahboubi K., Biedermann B.C., Carroll J.M., Pober J.S. IL-11 activates human endothelial cells to resist immune-mediated injury. J. Immunol. 2000; 164 (7): 3837–46. doi: 10.4049/jimmunol.164.7.3837.
  21. Mahboubi K., Li F., Plescia J., Kirkiles-Smith N.C., Mesri M., Du Y., Carroll J.M., Elias J.A., Altieri D.C., Pober J.S. Interleukin-11 up-regulates survivin expression in endothelial cells through a signal transducer and activator of transcription-3 pathway. Lab. Invest. 2001; 81 (3): 327–34. doi: 10.1038/labinvest.3780241.
  22. Lindkvist M., Zegeye M.M., Grenegård M., Ljungberg L.U. 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.
  23. Lim W.W., Corden B., Ng B., Vanezis K., D’Agostino G., Widjaja A.A., Song W.H., Xie C., Su L., Kwek X.Y., Tee N.G.Z., Dong J., Ko N.S.J., Wang M., Pua C.J., Jamal M.H., Soh B., Viswanathan S., Schafer S., Cook S.A. Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models. Sci. Rep. 2020; 10 (1): 17853. doi: 10.1038/s41598-020-74944-7.
  24. Zimmerman M.A., Selzman C.H., Reznikov L.L., Raeburn C.D., Barsness K., McIntyre R.C., Hamiel C.R., Harken A.H. Interleukin-11 attenuates human vascular smooth muscle cell proliferation. Am. J. Physiol. Heart Circ. Physiol. 2002; 283 (1): H175–80. doi: 10.1152/ajpheart.00987.2001.
  25. Lim W.W., Dong J., Ng B., Widjaja A.A., Xie C., Su L., Kwek X.Y., Tee N.G.Z., Jian Pua C., Schafer S., Viswanathan S., Cook S.A. Inhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan Syndrome. Circ. Res. 2022; 130 (5): 728–40. doi: 10.1161/CIRCRESAHA.121.320381.
  26. Lim W.W., Ng B., Widjaja A., Xie C., Su L., Ko N., Lim S.Y., Kwek X.Y., Lim S., Cook S.A., Schafer S. Transgenic interleukin 11 expression causes cross-tissue fibro-inflammation and an inflammatory bowel phenotype in mice. PLoS One. 2020; 15 (1): e0227505. doi: 10.1371/journal.pone.0227505.
  27. Schumacher D., Liehn E.A., Nilcham P., Mayan D.C., Rattanasopa C., Anand K., Crespo-Avilan G.E., Hernandez-Resendiz S., Singaraja R.R., Cook S.A., Hausenloy D.J. 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.
  28. Lebastchi A.H., Qin L., Khan S.F., Zhou J., Geirsson A., Kim R.W., Li W., Tellides G. Activation of human vascular cells decreases their expression of transforming growth factor-beta. Atherosclerosis. 2011; 219 (2): 417–24. doi: 10.1016/j.atherosclerosis.2011.07.121.
  29. Widjaja A.A., Viswanathan S., Jinrui D., Singh B.K., Tan J., Wei Ting J.G., Lamb D., Shekeran S.G., George B.L., Schafer S., Carling D., Adami E., Cook S.A. Molecular Dissection of Pro-Fibrotic IL11 Signaling in Cardiac and Pulmonary Fibroblasts. Front. Mol. Biosci. 2021; 8: 740650. doi: 10.3389/fmolb.2021.740650.
  30. Elshabrawy H.A., Volin M.V., Essani A.B., Chen Z., McInnes I.B., Van Raemdonck K., Palasiewicz K., Arami S., Gonzalez M., Ashour H.M., Kim S.J., Zhou G., Fox D.A., Shahrara S. IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells. Angiogenesis. 2018; 21 (2): 215–28. doi: 10.1007/s10456-017-9589-y.
  31. Guo Y.T., Lu Y.Y., Lu X., He S., Li S.J., Shao S., Zhou H.D., Wang R.Q., Li X.D., Gao P.J. 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.
  32. Sweeney M., O’Fee K., Villanueva-Hayes C., Rahman E., Lee M., Vanezis K., Andrew I., Lim W.W., Widjaja A., Barton P.J.R., Cook S.A.Cardiomyocyte-Restricted Expression of IL11 Causes Cardiac Fibrosis, Inflammation, and Dysfunction. Int. J. Mol. Sci. 2023; 24 (16): 12989. doi: 10.3390/ijms241612989.
  33. Obana M., Maeda M., Takeda K., Hayama A., Mohri T., Yamashita T., Nakaoka Y., Komuro I., Takeda K., Matsumiya G., Azuma J., Fujio Y. Therapeutic activation of signal transducer and activator of transcription 3 by interleukin-11 ameliorates cardiac fibrosis after myocardial infarction. Circulation. 2010; 121 (5): 684–91. doi: 10.1161/CIRCULATIONAHA.109.893677.
  34. Tamura Y., Kohno H., Mohri T., Fujio Y., Matsumiya G. The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model. Ann. Cardiothorac. Surg. 2018; 7 (1): 99–105. doi: 10.21037/acs.2017.09.11.
  35. Ragni M.V., Jankowitz R.C., Chapman H.L., Merricks E.P., Kloos M.T., Dillow A.M., Nichols T.C. A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease. Haemophilia. 2008; 14 (5): 968–77. doi: 10.1111/j.1365-2516.2008.01827. x.
  36. Liu N.W., Huang X., Liu S., Liu W.J., Wang H., Wang W.D., Lu Y. Elevated BNP caused by recombinant human interleukin-11 treatment in patients with chemotherapy-induced thrombocytopenia. Support Care Cancer. 2019; 27 (11): 4293–8. doi: 10.1007/s00520-019-04734-z.
  37. Ye J., Wang Z., Ye D., Wang Y., Wang M., Ji Q., Huang Y., Liu L., Shi Y., Shi L., Zeng T., Xu Y., Liu J., Jiang H., Lin Y., Wan J. Increased Interleukin-11 Levels Are Correlated with Cardiac Events in Patients with Chronic Heart Failure. Mediators Inflamm. 2019; 2019: 1575410. doi: 10.1155/2019/1575410.
  38. Xiang Y., Zhang Z., Xie C., Wang L., Wu Y., Zhan Y., Chen D. Serum Cat S, TSP-1, IL-11, BNP and sST2 Diagnostic and Prognostic Value in Chronic Heart Failure. Altern. Ther. Health. Med. 2022; 28 (4): 55–9.
  39. Milara J., Roger I., Montero P., Artigues E., Escrivá J., Cortijo J. IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis. Respir. Res. 2022; 23 (1): 313. doi: 10.1186/s12931-022-02241-0.
  40. Roger I., Milara J., Montero P., 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.
  41. Cong X., Tian B., Zhu X., Zhang X., Gu W., Zhao H., Hao S., Ning Z. Interleukin-11 Is Elevated in Patients with Atrial Fibrillation, Correlates with Serum Fibrosis Markers, and Represents a Therapeutic Target for Atrial Fibrosis. Cerebrovasc. Dis. 2023; 52 (5): 575–86. doi: 10.1159/000527740.
  42. Xu Y., Ye J., Wang M., Wang Y., Ji Q., Huang Y., Zeng T., Wang Z., Ye D., Jiang H., Liu J., Lin Y., Wan J. Increased interleukin-11 levels in thoracic aorta and plasma from patients with acute thoracic aortic dissection. Clin. Chim. Acta. 2018; 481: 193–9. doi: 10.1016/j.cca.2018.03.014.
  43. Fang H.Y., Ko W.J., Lin C.Y. Plasma interleukin 11 levels correlate with outcome of spontaneous intracerebral hemorrhage. Surg. Neurol. 2005; 64 (6): 511–7, discussion 517–8. doi: 10.1016/j.surneu.2005.03.018.
  44. Yang G., Shao G.F. Elevated serum IL-11, TNF α, and VEGF expressions contribute to the pathophysiology of hypertensive intracerebral hemorrhage (HICH). Neurol. Sci. 2016; 37 (8): 1253–9. doi: 10.1007/s10072-016-2576-z.
  45. Zhang B., Zhang H.X., Shi S.T., Bai Y.L., Zhe X., Zhang S.J., Li Y.J. Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury. Biomed. Pharmacother. 2019; 115: 108816. doi: 10.1016/j.biopha.2019.108816.
  46. Zuo D., Zheng Q., Xiao M., Wang X., Chen H., Xu J., Zhang Q., Xiong Y., Ye L., Feng Z. Anti-apoptosis effect of recombinant human interleukin-11 in neonatal hypoxic-ischemic rats through activating the IL-11Rα/STAT3 signaling pathway. J. Stroke Cerebrovasc. Dis. 2023; 32 (2): 106923. doi: 10.1016/j.jstrokecerebrovasdis.2022.106923.
  47. Airapetov M.I., Eresko S.O., Ignatova P.D., Lebedev A.A., Bychkov E.R., Shabanov P.D. Interleukin-11 in Pathologies of the Nervous System. Mol. Biol. 2023; 57 (1): 3–9. doi: 10.31857/S0026898423010020.

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