Natural Killer Cells as Critical Modulators of Heart Disease: Exploring Pathophysiological Mechanisms and Therapeutic Perspectives
-
Somayeh Shamlou
,
Jafar Kiani
,
Zahra Hasanpoor
,
Mohammad Tollabi
,
Fatemeh Norooznezhad
,
Saeedeh Torabi Goudarzi
,
Javad Verdi
,
Nasim Vousooghi
Abstract
Natural killer (NK) cells are crucial components of the innate immune system and have emerged as significant players in the pathogenesis of heart diseases. This review discusses recent findings regarding the multifaceted roles of NK cells in various cardiac conditions, including coronary artery disease, myocardial infarction, heart failure, myocarditis, and heart transplantation. It outlines the NK cell subsets, particularly CD56-bright and CD56-dim variations, their functional characteristics, cytokine profiles, and the inflammatory pathways they are involved. The review discusses both the beneficial and detrimental effects of NK cell activity on cardiac pathology by underlining their participation in immune regulation, tissue repair, and graft rejection dynamics. Additionally, we have addressed the impact of NK-cell–oriented environmental signals and discussed potential therapeutic approaches, such as immunomodulatory and anti-inflammatory strategies targeting NK cells. This review was therefore geared towards integrating available studies in understanding NK cell dynamics in heart disease and offering insights for future clinical interventions.
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2. Li H, Boulanger P. A survey of heart anomaly detection using ambulatory Electrocardiogram (ECG). Sensors. 2020;20(5):1461.
3. Dal Lin C, Tona F, Osto E. The crosstalk between the cardiovascular and the immune system. Vasc Biol. 2019;1(1):H83.
4. Kofler S, Nickel T, Weis M. Role of cytokines in cardiovascular diseases: a focus on endothelial responses to inflammation. Clin Sci. 2005;108(3):205-13.
5. Zitti B, Bryceson YT. Natural killer cells in inflammation and autoimmunity. Cytokine Growth Factor Rev. 2018;42:37-46.
6. Satoskar AR, Stamm LM, Zhang X, Okano M, David JR, Terhorst C, et al. NK cell-deficient mice develop a Th1-like response but fail to mount an efficient antigen-specific IgG2a antibody response. J Immunol. 1999;163(10):5298-302.
7. Adamo L, Rocha-Resende C, Prabhu SD, Mann DL. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol. 2020;17(5):269-85.
8. Bukowski JF, Woda BA, Habu S, Okumura K, Welsh RM. Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immun Balt. 1983;131(3):1531-8.
9. Shereck E, Satwani P, Morris E, Cairo MS. Human natural killer cells in health and disease. Pediatr Blood Cancer. 2007;49(5):615-23.
10. Yokoyama WM, Kim S, French AR. The dynamic life of natural killer cells. Annu Rev Immunol. 2004;22:405-29.
11. Vickers NJ. Animal communication: when i’m calling you, will you answer too? Curr Biol. 2017;27(14):R713-R5.
12. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633-40.
13. Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset. Am J Hematol. 2001;97(10):3146-51.
14. Poli A, Michel T, Thérésine M, Andrès E, Hentges F, Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunol. 2009;126(4):458-65.
15. Ansari AW, Ahmad F, Meyer-Olson D, Kamarulzaman A, Jacobs R, Schmidt RE. Natural killer cell heterogeneity: cellular dysfunction and significance in HIV-1 immuno-pathogenesis. Cell Mol Life Sci. 2015;72:3037-49.
16. Gumá M, Budt M, Sáez A, Brckalo T, Hengel H, Angulo A, et al. Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood. 2006;107(9):3624-31.
17. Goodier MR, Mela C, Steel A, Gazzard B, Bower M, Gotch F. NKG2C+ NK cells are enriched in AIDS patients with advanced-stage Kaposi's sarcoma. J Virol. 2007;81(1):430-3.
18. López-Botet M, Muntasell A, Vilches C, editors. The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Semin Immunol. 2014;26(2):145-151.
19. Hak Ł, Myśliwska J, Więckiewicz J, Szyndler K, Trzonkowski P, Siebert J, et al. NK cell compartment in patients with coronary heart disease. Immun Ageing. 2007;4:1-8.
20. Bonaccorsi I, Spinelli D, Cantoni C, Barillà C, Pipitò N, De Pasquale C, et al. Symptomatic carotid atherosclerotic plaques are associated with increased infiltration of natural killer (NK) cells and higher serum levels of NK activating receptor ligands. Front Immunol. 2019;10:1503.
21. Jonasson L, Backteman K, Ernerudh J. Loss of natural killer cell activity in patients with coronary artery disease. Atherosclerosis. 2005;183(2):316-21.
22. Li W, Lidebjer C, Yuan X-M, Szymanowski A, Backteman K, Ernerudh J, et al. NK cell apoptosis in coronary artery disease: relation to oxidative stress. Atherosclerosis. 2008;199(1):65-72.
23. Hou N, Zhao D, Liu Y, Gao L, Liang X, Liu X, et al. Increased expression of T cell immunoglobulin-and mucin domain-containing molecule-3 on natural killer cells in atherogenesis. Atheroscler. 2012;222(1):67-73.
24. Backteman K, Ernerudh J, Jonasson L. Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation. Clin Exp Immunol. 2014;175(1):104-12.
25. Yan W, Zhou L, Wen S, Duan Q, Huang F, Tang Y, et al. Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris. Int J Clin Exp Pathol. 2015;8(11):14667.
26. Kanda T, Ohshima S, Yuasa K, Watanabe T, Suzuki T, Murata K. Idiopathic myocarditis associated with T-cell subset changes and depressed natural killer activity. Jpn Heart J. 1990;31(5):741-4.
27. Müller I, Janson L, Sauter M, Pappritz K, Linthout SV, Tschöpe C, et al. Myeloid-derived suppressor cells restrain natural killer cell activity in acute coxsackievirus B3-induced myocarditis. Viruses. 2021;13(5):889.
28. Persic V, Ruzic A, Miletic B, Samsa DT, Rakic M, Raljevic D, et al. Granulysin expression in lymphocytes that populate the peripheral blood and the myocardium after an acute coronary event. Scand J Immunol. 2012;75(2):231-42.
29. Romo N, Fitó M, Gumá M, Sala J, García C, Ramos R, et al. Association of atherosclerosis with expression of the LILRB1 receptor by human NK and T-cells supports the infectious burden hypothesis. Arterioscler Thromb Vasc Biol. 2011;31(10):2314-21.
30. Yao H-C, Liu S-Q, Yu K, Zhou M, Wang L-X. Interleukin-2 enhances the cytotoxic activity of circulating natural killer cells in patients with chronic heart failure. Heart Vessels. 2009;24(4).
31. Nemlander A, Saksela E, Häyry P. Are “natural killer” cells involved in allograft rejection? Eur J Immunol. 1983;13(4):348-50.
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| Issue | Articles in Press | |
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| Keywords | ||
| Coronary artery disease Heart diseases Heart transplantations Myocardial infarctions Natural killer cells | ||
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How to Cite
1.
Shamlou S, Kiani J, Hasanpoor Z, Tollabi M, Norooznezhad F, Torabi Goudarzi S, Verdi J, Vousooghi N. Natural Killer Cells as Critical Modulators of Heart Disease: Exploring Pathophysiological Mechanisms and Therapeutic Perspectives. Iran J Allergy Asthma Immunol. 2025;:1-14.
