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Current Atherosclerosis Reports
Published in: Current Atherosclerosis Reports 6/2017

01-06-2017 | Evidence Based Medicine (L. Roever, Section Editor)

Role of Inflammation in Heart Failure

Authors: Lily F. Shirazi, Joe Bissett, Francesco Romeo, Jawahar L. Mehta

Published in: Current Atherosclerosis Reports | Issue 6/2017

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Abstract

Purpose of Review

This paper aims to discuss the interactions between inflammatory cytokines, immune cells, and heart failure (HF). The association of heart failure with inflammation has led to multiple studies on anti-inflammatory agents in acute and chronic heart failure.

Recent Findings

Recent findings have implicated leukocytes subclasses and multiple inflammatory mediators in the progression of heart failure and cardiovascular disease. Studies have discovered further details on the interaction between immune cells—particularly macrophages and lymphocytes—and inflammation. There are both cell-mediated and cytokine-mediated pathways of inflammation, which are interconnected. Additionally, a number of markers have been used and studied in heart failure disease progression.

Summary

In this review, we discuss inflammatory biomarkers and immune cell mediators involved in HF. We will focus on the correlations and role of these inflammatory mediators in the genesis of HF. We will also discuss the evidence on beneficial effects of anti-inflammatory agents in the setting of chronic HF.
Literature
1.
Stewart S, MacIntyre K, Capewell S, McMurray JJ. Heart failure and the aging population: an increasing burden in the 21st century. Heart. 2003;89(1):49–53.CrossRefPubMedPubMedCentral
2.
Seta Y, Shan K, Bozkurt B, Oral H, Mann DL. Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail. 1996;2:243–9.CrossRefPubMed
3.
• Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ Res. 2015;116:1254–68. This review discusses the role of inflammation and heart failure, in light of new understanding of innate immunity. CrossRefPubMedPubMedCentral
4.
Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323(4):236–41.CrossRefPubMed
5.
Kubota T, Miyagishima M, Alvarez RJ, et al. Expression of proinflammatory cytokines in the failing human heart: comparison of recent-onset and end-stage congestive heart failure. J Heart Lung Transplant. 2000;19(9):819–24.CrossRefPubMed
6.
Awad AE, Kandalam V, Chakrabarti S, et al. Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner. Am J Physiol Cell Physiol. 2010;298(3):C679–92.CrossRefPubMed
7.
Deswal A, Bozkurt B, Seta Y, Parilti-Eiswirth S, Hayes FA, Blosch C, Mann DL. Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, etanercept) in patients with advanced heart failure. Circulation. 1999;99:3224–6.CrossRefPubMed
8.
Van Tassell BW, Seropian IM, Toldo S, Mezzaroma E, Abbate A. Interleukin-1beta induces a reversible cardiomyopathy in the mouse. Inflamm Res. 2013;62(7):637–40.CrossRefPubMed
9.
Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE. Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med. 1996;183(3):949–58.CrossRefPubMed
10.
Van Tassell BW, Arena RA, Toldo S, et al. Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS One. 2012;7(3):e33438.CrossRefPubMedPubMedCentral
11.
Fischer P, Hilfiker-Kleiner D. Role of gp130-mediated signalling pathways in the heart and its impact on potential therapeutic aspects. Br J Pharmacol. 2008;153(Suppl 1):S414–27.PubMedPubMedCentral
12.
Fischer P, Hilfiker-Kleiner D. Survival pathways in hypertrophy and heart failure: the gp130-STAT axis. Basic Res Cardiol. 2007;102(5):393–411.CrossRefPubMed
13.
Hilfiker-Kleiner D, Shukla P, Klein G, et al. Continuous glycoprotein-130-mediated signal transducer and activator of transcription-3 activation promotes inflammation, left ventricular rupture, and adverse outcome in subacute myocardial infarction. Circulation. 2010;122(2):145–55.CrossRefPubMed
14.
15.
Smart N, Mojet MH, Latchman DS, Marber MS, Duchen MR, Heads RJ. IL-6 induces PI 3-kinase and nitric oxide-dependent protection and preserves mitochondrial function in cardiomyocytes. Cardiovasc Res. 2006;69(1):164–77.CrossRefPubMed
16.
Swerdlow DI, Holmes MV, Kuchenbaecker KB, Engmann JE, et al. Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012;379(9822):1214–24.CrossRefPubMed
17.
Nymo SH, Hulthe J, Ueland T, McMurray J, Wikstrand J, Askevold ET, Yndestad A, Gullestad L, Aukrust P. Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA. Eur J Heart Fail. 2001;16(1):68–75.CrossRef
18.
Trofimov ES, Poskrebysheva AS. Study on activity of inflammatory factors in patients with chronic heart failure depending on the stage of the disease and NYHA class. Bull Exp Biol Med. 2015;158(5):614–6.CrossRefPubMed
19.
Li XF, Pan D, Zhang WL, Zhou J, Liang JJ. Association of NT-proBNP and interleukin-17 levels with heart failure in elderly patients. Genet Mol Res. 2016;15(2).
20.
Zhou SF, Yuan J, Liao MY, Xia N, Tang TT, Li JJ, Jiao J, Dong WY, Nie SF, Zhu ZF, Zhang WC, Lv BJ, Xiao H, Wang Q, Tu X, Liao YH, Shi GP, Cheng X. IL-17A promotes ventricular remodeling after myocardial infarction. J Mol Med (Berl). 2014;92(10):1105–16.CrossRef
21.
Pomerantz BJ, Reznikov LL, Harken AH, Dinarello CA. Inhibition of caspase I reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1beta. Proc Natl Acad Sci U S A. 2001;98:2871–6.CrossRefPubMedPubMedCentral
22.
Smithgall MD, Comeau MR, Yoon BR, Kaufman D, Armitage R, Smith DE. IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol. 2008;20(8):1019–30.CrossRefPubMed
23.
Komai-Koma M, Wang E, Kurowska-Stolarska M, Li D, McSharry C, Xu D. Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12. Immunobiology. 2016;221(3):412–7.CrossRefPubMedPubMedCentral
24.
Roselló-Lletí E, Rivera M, Bertomeu V, Cortés R, Jordán A, González-Molina A. Interleukin-4 and cardiac fibrosis in patients with heart failure. Rev Esp Cardiol. 2007;60(7):777–80.CrossRefPubMed
25.
Peng H, Sarwar Z, Yang XP, Peterson EL, Xu J, Janic B, Rhaleb N, Carretero OA, Rhaleb NE. Profibrotic role for interleukin-4 in cardiac remodeling and dysfunction. Hypertension. 2015;66(3):582–9.CrossRefPubMedPubMedCentral
26.
Amir O, Rogowski O, David M, Lahat N, Wolff R, Lewis BS. Circulating interleukin-10: association with higher mortality in systolic heart failure patients with elevated tumor necrosis factor-alpha. Isr Med Assoc J. 2010;12(3):158–62.PubMed
27.
Giomarelli P, Scolletta S, Borrelli E, Biagioli B. Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10. Ann Thorac Surg. 2003;76(1):117–23.CrossRefPubMed
28.
Adampoulos S, Parissis JT, Parraskevaidis I, Karatzas D, Livanis E, Georgiadis M, Karavolias G, Mitropoulos D, Degiannis D, Kremastinos DT. Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy. Eur Heart J. 2003;24(24):2186–96.CrossRef
29.
Edgley AJ, Krum H, Kelly DJ. Targeting fibrosis for the treatment of heart failure: a role for transforming growth factor-β. Cardiovasc Ther. 2012;30(1):e30–40.CrossRefPubMed
30.
Frantz S, Hu K, Adamek A, Wolf J, Sallam A, Maier SK, et al. Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res Cardiol. 2008;103:485–92.CrossRefPubMed
31.
Vasan RS, Sullivan LM, Roubenoff R, Dinarello CA, Harris T, Benjamin EJ, Sawyer DB, Levy D, Wilson PW, D’Agostino RB, Framingham Heart Study. Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation. 2003;107:1486–91.CrossRefPubMed
32.
Van der Velde AR, Gullestad L, Ueland T, Aukrust P, Guo Y, Adourian A, Muntendam P, Van Veldhuisen DJ, de Boer RA. Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH. Circ Heart Fail. 2013;6(2):219–26.CrossRefPubMed
33.
Edelmann F, Holzendorf V, Wachter R, Nolte K, Schmidt AG, Kraigher-Krainer E, Duvinage A, Unkelbach I, Düngen HD, Tschöpe C, Hermann-Lingen C, Halle M, Hasenfuss G, Gelbrich G, Stough WG, Pieske BM. Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial. Eur J Heart Fail. 2015;17:214–23.CrossRefPubMed
34.
McEvoy JW, Chen Y, Halushka MK, Christenson E, Ballantyne CM, Blumenthal RS, Christenson RH, Selvin E. Galectin-3 and risk of heart failure and death in blacks and whites. J Am Heart Assoc. 2016;5(5).
35.
36.
Felker GM, Fiuzat M, Thompson V, Shaw LK, Neely ML, Adams KF, Whellan DJ, Donahue MP, Ahmad T, Kitzman DW, Piña IL, Zannad F, Kraus WE, O’Conner CM. Soluble ST2 in ambulatory patients with heart failure: association with functional capacity and long-term outcomes. Circ Heart Fail. 2013;6(6):1172–9.CrossRefPubMedPubMedCentral
37.
• Frieler RA, Mortensen RM. Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling. Circulation. 2015;131(11):1019–30. This review discusses the interaction between immune cells and inflammatory signaling, with implications toward therapeutic targets. CrossRefPubMedPubMedCentral
38.
• Mehta JL, Pothineni NVK. Inflammation in heart failure: the holy grail? Hypertension. 2016;68:27–9. This review discusses the different effects of inflammation in acute versus chronic setting, particularly emphasizing the role of regulatory T cells. CrossRefPubMed
39.
•• Libby P, Nahrendorf M, Swirski FK. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “cardiovascular continuum.”. J Am Coll Cardiol. 2016;67(9):1091–103. This review discusses the role of immune cells and inflammatory signaling in cardiovascular diseases, emphasizing the role of leukocytes. CrossRefPubMedPubMedCentral
40.
41.
Aharinejad S, Abraham D, Paulus P, Zins K, Hofmann M, Michlits W, Gyöngyösi M, Macfelda K, Lucas T, Trescher K, Grimm M, Stanley ER. Colony-stimulating factor-1 transfection of myoblasts improves the repair of the failing myocardium following autologous myoblast transplantation. Cardiovasc Res. 2008;79:395–404.CrossRefPubMedPubMedCentral
42.
Baldeviano GC, Barin JG, Talor MV, Srinivasan S, Bedja D, Zheng D, Gabrielson K, Iwakura Y, Rose NR, Cihakova D. Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy. Circ Res. 2010;106:1646–55.CrossRefPubMed
43.
Kain D, Amit U, Yagil C, Landa N, Naftali-Shani- N, Molotski N, Aviv V, Feinberg MS, Goitein O, Kushnir T, Konen E, Epstein FH, Yagil Y, Leor J. Macrophages dictate the progression and manifestation of hypertensive heart disease. Int J Cardiol. 2016;203:381–95.CrossRefPubMed
44.
Leuschner F, Courties G, Dutta P, et al. Silencing of CCR2 in myocarditis. Eur Heart J. 2015;36:1478–88.CrossRefPubMed
45.
Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Anti-TNF therapy against congestive heart failure investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107(25):3133–40.CrossRefPubMed
46.
Mann DL, McMurray JJV, Packer M, et al. Targeted anti-cytokine therapy in patients with chronic heart failure: results of the Randomized Etancercept Worldwide Evaluation (RENEWAL). Circulation. 2004;109:1594–602.CrossRefPubMed
47.
Gullestad L, Ueland T, Fjeld JG, et al. Effect of thalidomide on cardiac remodeling in chronic heart failure: results of a double-blind, placebo-controlled study. Circulation. 2005;112:3408–14.CrossRefPubMed
48.
Parrillo JE, Cunnion RE, Epstein SE, Parker ME, Suffredini AF, Brenner M, Schaer GL, Palmeri ST, Cannon RO, Alling D, Wittes JT, Ferrans VJ, Rodriguez ER, Fauci AS. A prospective randomized controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med. 1989;321:1061–8.CrossRefPubMed
49.
Skudicky D, Bergemann A, Sliwa K, Candy G, Sareli P. Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study. Circulation. 2001;103(8):1083–8.CrossRefPubMed
50.
Sliwa K, Skudicky D, Candy G, Wisenbaugh T, Sareli P. Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy. Lancet. 1998;351:1091–3.CrossRefPubMed
51.
Sliwa K, Woodiwiss A, Candy G, Badenhorst D, Libhaber C, Norton G, Skudicky D, Sareli P. Effects of pentoxifylline on left-ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol. 2002;90:1118–22.CrossRefPubMed
52.
Sliwa K, Woodiwiss A, Kone VN, Candy G, Badenhorst D, Norton G, Zambakides C, Peters F, Essop R. Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study. Circulation. 2004;109:750–5.CrossRefPubMed
53.
Torre-Amione G, Anker SD, Bourge RC, et al. Advanced chronic heart failure clinical assessment of immune modulation therapy investigators. Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomized trial. Lancet. 2008;371:228–36.CrossRefPubMed
54.
Gullestad L, Aass H, Fjeld JG, Wikeby L, Andreassen AK, Ihlen H, Simonsen S, Kjekshus J, Nitter-Hauge S, Ucland T, Lien E, Frøland SS, Aukrust P. Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation. 2001;103:220–5.CrossRefPubMed
55.
McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G, Gass A, Janosko K, Tokarczyk T, Kessler P, Mann DL, Feldman AM. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation. 2001;103:2254–9.CrossRefPubMed
56.
Moreira DM, Vieira JL, Gottschall CA. The effects of METhotrexate therapy on the physical capacity of patients with ISchemia heart failure: a randomized double-blind, placebo-controlled trial (METIS trial). J Card Fail. 2009;15:828–34.CrossRefPubMed
Metadata
Title
Role of Inflammation in Heart Failure
Authors
Lily F. Shirazi
Joe Bissett
Francesco Romeo
Jawahar L. Mehta
Publication date
01-06-2017
Publisher
Springer US
Published in
Current Atherosclerosis Reports / Issue 6/2017
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-017-0660-3

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