Portal de Periódicos da CAPES

Heart Inflammation

2019; Elsevier BV; Volume: 189; Issue: 8 Linguagem: Inglês

10.1016/j.ajpath.2019.04.009

1525-2191

Francisco Carrillo‐Salinas, Njabulo Ngwenyama, Marina Anastasiou, Kuljeet Kaur, Pilar Alcaide,

Signaling Pathways in Disease

Heart failure (HF) has been traditionally viewed as a disease of the cardiac muscle associated with systemic inflammation. Burgeoning evidence implicates immune effector mechanisms that include immune cell activation and trafficking to the heart. Immune cell infiltration in the myocardium can have adverse effects in the heart and contribute to the pathogenesis of HF. Both innate and adaptive immunity operate sequentially, and the specificity of these responses depends on the initial trigger sensed by the heart. Although the role of the immune system in the initial inflammatory response to infection and injury is well studied, what sets the trajectory to HF from different etiologies and the role of immunity once HF has been established is less understood. Herein, we review experimental and clinical knowledge of cardiac inflammation induced by different triggers that often result in HF from different etiologies. We focus on the mechanisms of immune cell activation systemically and on the pathways immune cells use to traffic to the heart. Heart failure (HF) has been traditionally viewed as a disease of the cardiac muscle associated with systemic inflammation. Burgeoning evidence implicates immune effector mechanisms that include immune cell activation and trafficking to the heart. Immune cell infiltration in the myocardium can have adverse effects in the heart and contribute to the pathogenesis of HF. Both innate and adaptive immunity operate sequentially, and the specificity of these responses depends on the initial trigger sensed by the heart. Although the role of the immune system in the initial inflammatory response to infection and injury is well studied, what sets the trajectory to HF from different etiologies and the role of immunity once HF has been established is less understood. Herein, we review experimental and clinical knowledge of cardiac inflammation induced by different triggers that often result in HF from different etiologies. We focus on the mechanisms of immune cell activation systemically and on the pathways immune cells use to traffic to the heart. Heart failure (HF) is the clinical manifestation of numerous forms of cardiovascular disease that impact the ability of the heart to efficiently pump blood to organs and tissues. It is also the predominant cause of mortality in the United States, affecting 6.5 million of Americans. Prognosis after the first hospital admission is poor, with >50% mortality rate within 5 years.1Benjamin E.J. Virani S.S. Callaway C.W. Chamberlain A.M. Chang A.R. Cheng S. et al.American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics-2018 update: a report from the American Heart Association.Circulation. 2018; 137: e67-e492Crossref PubMed Scopus (4465) Google Scholar For decades, research using experimental models of HF and data from clinical studies supported the concept that HF was a disease of the cardiac muscle, dominated mainly by aberrant activation of the neurohormonal and sympathetic systems. Early clinical observations that date back to the 1950s initially reported an association of C-reactive protein with different etiologies of HF that suggested an inflammatory component to be considered in the complexity of HF.2Elster S.K. Braunwald E. Wood H.F. A study of C-reactive protein in the serum of patients with congestive heart failure.Am Heart J. 1956; 51: 533-541Crossref PubMed Scopus (77) Google Scholar These studies were followed by larger ones in the cytokine era, demonstrating an elevation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), in HF patients. However, therapeutic modulation of TNF-α was deemed unsuccessful in patients with HF in large clinical trials, indicating the need of further understanding the inflammatory mechanisms involved in achieving immunomodulation in HF.3Mann D.L. Innate immunity and the failing heart: the cytokine hypothesis revisited.Circ Res. 2015; 116: 1254-1268Crossref PubMed Scopus (428) Google Scholar, 4Chung E.S. Packer M. Lo K.H. Fasanmade A.A. Willerson J.T. Anti-TNF Therapy Against Congestive Heart Failure InvestigatorsRandomized, 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: 3133-3140Crossref PubMed Scopus (1240) Google Scholar, 5Mann D.L. McMurray J.J. Packer M. Swedberg K. Borer J.S. Colucci W.S. Djian J. Drexler H. Feldman A. Kober L. Krum H. Liu P. Nieminen M. Tavazzi L. van Veldhuisen D.J. Waldenstrom A. Warren M. Westheim A. Zannad F. Fleming T. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL).Circulation. 2004; 109: 1594-1602Crossref PubMed Scopus (963) Google Scholar, 6Schnoor M. Alcaide P. Voisin M.B. van Buul J.D. Recruitment of immune cells into inflamed tissues: consequences for endothelial barrier integrity and tissue functionality.Mediators Inflamm. 2016; 2016: 1561368Crossref PubMed Scopus (10) Google Scholar This review adds to the complexity of HF with a new view involving immune cells and pathways as orchestrators of local inflammation in the heart that may contribute to the initiation, maintenance, and progression of HF. Proinflammatory cytokines, bacterial endotoxins, and oxidized low-density lipoprotein, reported circulating in HF patients, induce the expression of vascular endothelial cell adhesion molecules and chemoattractants that contribute to leukocyte recruitment. Leukocytes roll on the activated endothelium by leukocyte selectin ligand–endothelial selectin and leukocyte α4β1 integrin-endothelial vascular cell adhesion molecule 1–mediated interactions. This step is followed by leukocyte integrin-endothelial intercellular adhesion molecule 1 (ICAM-1) adhesion and locomotion on the endothelial-cell vessel wall. These interactions precede leukocyte firm arrest near endothelial cell-cell junctions and transendothelial migration and extravasation into tissues,7Schnoor M. Alcaide P. Voisin M.B. van Buul J.D. Crossing the vascular wall: common and unique mechanisms exploited by different leukocyte subsets during extravasation.Mediators Inflamm. 2015; 2015: 946509Crossref PubMed Scopus (112) Google Scholar a process in which ICAM-1 and several endothelial cell molecules participate. Different types of leukocytes, which include neutrophils, monocytes, and lymphocytes, have all been reported in the inflamed heart. Although special and temporal differences exist, depending on the initial stimuli triggering heart inflammation, neutrophils are generally the first ones being recruited. Monocytes, classified as proinflammatory or anti-inflammatory on the basis of Ly6C high or low expression, respectively, and T cells follow neutrophils.7Schnoor M. Alcaide P. Voisin M.B. van Buul J.D. Crossing the vascular wall: common and unique mechanisms exploited by different leukocyte subsets during extravasation.Mediators Inflamm. 2015; 2015: 946509Crossref PubMed Scopus (112) Google Scholar, 8Jones D.P. True H.D. Patel J. Leukocyte trafficking in cardiovascular disease: insights from experimental models.Mediators Inflamm. 2017; 2017: 9746169Crossref PubMed Scopus (32) Google Scholar T-cell progenitors arise from the bone marrow and populate the thymus, where self-reactive T cells are eliminated and non–self-reactive T cells mature and migrate to secondary lymphoid organs (spleen and lymph nodes) and respond to antigens presented by antigen-presenting cells (APCs) to mount an immune response. Effector CD8+ cytotoxic T cells and subsets of CD4+ T cells, which include T-helper (Th) cells and T-regulatory (Treg) cells, cooperate with innate cells during the immune response. Treg and Th cells are characterized by the expression of signature transcription factors, the production of different cytokines, and distinct effector functions. Th type 1 (Th1) cells produce interferon (IFN)-γ and activate macrophages and other cells, whereas Th type 17 (Th17) cells produce IL-17, IL-21, and IL-22 and promote neutrophil functions, and Th type 2 (Th2) cells produce IL-4, IL-5, and IL-13 and promote antibody production in B cells.9Kunicki M.A. Amaya Hernandez L.C. Davis K.L. Bacchetta R. Roncarolo M.G. Identity and diversity of human peripheral Th and T regulatory cells defined by single-cell mass cytometry.J Immunol. 2018; 200: 336-346Crossref PubMed Scopus (52) Google Scholar These evolutionary mechanisms, in place to protect us from several infectious agents, turn out to be critically associated with acute and chronic heart inflammation, and may define the transition to the different etiologies of HF. Leukocyte differences in responsiveness to certain chemokines and in the expression/activation of adhesion molecules are thought to be induced by the type of inflammatory trigger.6Schnoor M. Alcaide P. Voisin M.B. van Buul J.D. Recruitment of immune cells into inflamed tissues: consequences for endothelial barrier integrity and tissue functionality.Mediators Inflamm. 2016; 2016: 1561368Crossref PubMed Scopus (10) Google Scholar We are beginning to understand the specific mechanisms involved in the recruitment of different leukocytes to the heart and whether common or distinct pathways exist for specific leukocytes that contribute to the different etiologies of HF. Herein, we review the current knowledge from experimental models and humans with HF in the complexity of heart inflammation and the leukocyte recruitment mechanisms that may initiate, sustain, or perpetuate HF from different etiologies. We highlight similarities and differences in the activation of immune cells that participate in heart inflammation, which need to be taken into consideration for immunomodulation in HF. The immune system is the main driver of the protective inflammatory response necessary for host defense from infections, wound healing and tissue repair, and maintaining immune tolerance to self-antigens, all functions indispensable for survival. However, continuous active immune responses typically result in chronic inflammation, characterized as inflammation extending over time, with tissue destruction and repair occurring simultaneously. In contrast to mucosal and connective tissues, such as the lung, the gastrointestinal tract, or the skin, which are in constant contact with the environment, the heart is not exposed to the outside world. The heart stromal cells also differ from those in other organs in their limited ability for self-renewal. Thus, a small degree of inflammation induced by sterile or infectious insults has fatal consequences in resident cells, which often lead to fatal arrythmias, sudden death, or HF.10Taqueti V.R. Mitchell R.N. Lichtman A.H. Protecting the pump: controlling myocardial inflammatory responses.Annu Rev Physiol. 2006; 68: 67-95Crossref PubMed Scopus (62) Google Scholar Fortunately, there are mechanisms in place to protect the heart from this and sustain life. The current understanding of the complex immune response in the different etiologies of HF is reviewed in this section (Figure 1). Table 1 summarizes the immune cells that are recruited during heart inflammation and the main molecules involved in the process.11Sikder S. Williams N.L. Sorenson A.E. Alim M.A. Vidgen M.E. Moreland N.J. Rush C.M. Simpson R.S. Govan B.L. Norton R.E. Cunningham M.W. McMillan D.J. Sriprakash K.S. Ketheesan N. Group G. Streptococcus induces an autoimmune carditis mediated by interleukin 17A and interferon gamma in the Lewis rat model of rheumatic heart disease.J Infect Dis. 2018; 218: 324-335Crossref PubMed Scopus (23) Google Scholar, 12Wolf D. Li J. Ley K. HGF guides T cells into the heart.Immunity. 2015; 42: 979-981Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 13Shim S.H. Kim D.S. Cho W. Nam J.H. Coxsackievirus B3 regulates T-cell infiltration into the heart by lymphocyte function-associated antigen-1 activation via the cAMP/Rap1 axis.J Gen Virol. 2014; 95: 2010-2018Crossref PubMed Scopus (10) Google Scholar, 14Leuschner F. Courties G. Dutta P. Mortensen L.J. Gorbatov R. Sena B. Novobrantseva T.I. Borodovsky A. Fitzgerald K. Koteliansky V. Iwamoto Y. Bohlender M. Meyer S. Lasitschka F. Meder B. Katus H.A. Lin C. Libby P. Swirski F.K. Anderson D.G. Weissleder R. Nahrendorf M. Silencing of CCR2 in myocarditis.Eur Heart J. 2015; 36: 1478-1488Crossref PubMed Scopus (73) Google Scholar, 15Marchant D.J. McManus B.M. Regulating viral myocarditis: allografted regulatory T cells decrease immune infiltration and viral load.Circulation. 2010; 121: 2609-2611Crossref PubMed Scopus (14) Google Scholar, 16Shi Y. Fukuoka M. Li G. Liu Y. Chen M. Konviser M. Chen X. Opavsky M.A. Liu P.P. Regulatory T cells protect mice against coxsackievirus-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway.Circulation. 2010; 121: 2624-2634Crossref PubMed Scopus (87) Google Scholar, 17Talvani A. Rocha M.O. Barcelos L.S. Gomes Y.M. Ribeiro A.L. Teixeira M.M. Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy.Clin Infect Dis. 2004; 38: 943-950Crossref PubMed Scopus (106) Google Scholar, 18Gomes J.A. Bahia-Oliveira L.M. Rocha M.O. Martins-Filho O.A. Gazzinelli G. Correa-Oliveira R. Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a Th1-specific immune response.Infect Immun. 2003; 71: 1185-1193Crossref PubMed Scopus (231) Google Scholar, 19Silverio J.C. Pereira I.R. Cipitelli Mda C. Vinagre N.F. Rodrigues M.M. Gazzinelli R.T. Lannes-Vieira J. CD8+ T-cells expressing interferon gamma or perforin play antagonistic roles in heart injury in experimental Trypanosoma cruzi-elicited cardiomyopathy.PLoS Pathog. 2012; 8: e1002645Crossref PubMed Scopus (75) Google Scholar, 20Alcaide P. Fresno M. The Trypanosoma cruzi membrane mucin AgC10 inhibits T cell activation and IL-2 transcription through L-selectin.Int Immunol. 2004; 16: 1365-1375Crossref PubMed Scopus (28) Google Scholar, 21Michailowsky V. Celes M.R. Marino A.P. Silva A.A. Vieira L.Q. Rossi M.A. Gazzinelli R.T. Lannes-Vieira J. Silva J.S. Intercellular adhesion molecule 1 deficiency leads to impaired recruitment of T lymphocytes and enhanced host susceptibility to infection with Trypanosoma cruzi.J Immunol. 2004; 173: 463-470Crossref PubMed Scopus (31) Google Scholar, 22King K.R. Aguirre A.D. Ye Y.X. Sun Y. Roh J.D. Ng Jr., R.P. Kohler R.H. Arlauckas S.P. Iwamoto Y. Savol A. Sadreyev R.I. Kelly M. Fitzgibbons T.P. Fitzgerald K.A. Mitchison T. Libby P. Nahrendorf M. Weissleder R. IRF3 and type I interferons fuel a fatal response to myocardial infarction.Nat Med. 2017; 23: 1481-1487Crossref PubMed Scopus (235) Google Scholar, 23Cao D.J. Schiattarella G.G. Villalobos E. Jiang N. May H.I. Li T. Chen Z.J. Gillette T.G. Hill J.A. Cytosolic DNA sensing promotes macrophage transformation and governs myocardial ischemic injury.Circulation. 2018; 137: 2613-2634Crossref PubMed Scopus (91) Google Scholar, 24Nahrendorf M. Swirski F.K. Aikawa E. Stangenberg L. Wurdinger T. Figueiredo J.L. Libby P. Weissleder R. Pittet M.J. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions.J Exp Med. 2007; 204: 3037-3047Crossref PubMed Scopus (1634) Google Scholar, 25Majmudar M.D. Keliher E.J. Heidt T. Leuschner F. Truelove J. Sena B.F. Gorbatov R. Iwamoto Y. Dutta P. Wojtkiewicz G. Courties G. Sebas M. Borodovsky A. Fitzgerald K. Nolte M.W. Dickneite G. Chen J.W. Anderson D.G. Swirski F.K. Weissleder R. Nahrendorf M. Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice.Circulation. 2013; 127: 2038-2046Crossref PubMed Scopus (221) Google Scholar, 26Kaikita K. Hayasaki T. Okuma T. Kuziel W.A. Ogawa H. Takeya M. Targeted deletion of CC chemokine receptor 2 attenuates left ventricular remodeling after experimental myocardial infarction.Am J Pathol. 2004; 165: 439-447Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar, 27Hofmann U. Beyersdorf N. Weirather J. Podolskaya A. Bauersachs J. Ertl G. Kerkau T. Frantz S. Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice.Circulation. 2012; 125: 1652-1663Crossref PubMed Scopus (316) Google Scholar, 28Saxena A. Bujak M. Frunza O. Dobaczewski M. Gonzalez-Quesada C. Lu B. Gerard C. Frangogiannis N.G. CXCR3-independent actions of the CXC chemokine CXCL10 in the infarcted myocardium and in isolated cardiac fibroblasts are mediated through proteoglycans.Cardiovasc Res. 2014; 103: 217-227Crossref PubMed Scopus (53) Google Scholar, 29Weirather J. Hofmann U.D. Beyersdorf N. Ramos G.C. Vogel B. Frey A. Ertl G. Kerkau T. Frantz S. Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation.Circ Res. 2014; 115: 55-67Crossref PubMed Scopus (406) Google Scholar, 30Anzai A. Anzai T. Nagai S. Maekawa Y. Naito K. Kaneko H. Sugano Y. Takahashi T. Abe H. Mochizuki S. Sano M. Yoshikawa T. Okada Y. Koyasu S. Ogawa S. Fukuda K. Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling.Circulation. 2012; 125: 1234-1245Crossref PubMed Scopus (222) Google Scholar, 31Choo E.H. Lee J.H. Park E.H. Park H.E. Jung N.C. Kim T.H. Koh Y.S. Kim E. Seung K.B. Park C. Hong K.S. Kang K. Song J.Y. Seo H.G. Lim D.S. Chang K. Infarcted myocardium-primed dendritic cells improve remodeling and cardiac function after myocardial infarction by modulating the regulatory T cell and macrophage polarization.Circulation. 2017; 135: 1444-1457Crossref PubMed Scopus (108) Google Scholar, 32Van der Borght K. Scott C.L. Nindl V. Bouche A. Martens L. Sichien D. Van Moorleghem J. Vanheerswynghels M. De Prijck S. Saeys Y. Ludewig B. Gillebert T. Guilliams M. Carmeliet P. Lambrecht B.N. Myocardial infarction primes autoreactive T cells through activation of dendritic cells.Cell Rep. 2017; 18: 3005-3017Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 33Dobaczewski M. Xia Y. Bujak M. Gonzalez-Quesada C. Frangogiannis N.G. CCR5 signaling suppresses inflammation and reduces adverse remodeling of the infarcted heart, mediating recruitment of regulatory T cells.Am J Pathol. 2010; 176: 2177-2187Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar, 34Bujak M. Dobaczewski M. Gonzalez-Quesada C. Xia Y. Leucker T. Zymek P. Veeranna V. Tager A.M. Luster A.D. Frangogiannis N.G. Induction of the CXC chemokine interferon-gamma-inducible protein 10 regulates the reparative response following myocardial infarction.Circ Res. 2009; 105: 973-983Crossref PubMed Scopus (104) Google Scholar, 35Ridker P.M. Everett B.M. Thuren T. MacFadyen J.G. Chang W.H. Ballantyne C. Fonseca F. Nicolau J. Koenig W. Anker S.D. Kastelein J.J.P. Cornel J.H. Pais P. Pella D. Genest J. Cifkova R. Lorenzatti A. Forster T. Kobalava Z. Vida-Simiti L. Flather M. Shimokawa H. Ogawa H. Dellborg M. Rossi P.R.F. Troquay R.P.T. Libby P. Glynn R.J. Group C.T. Antiinflammatory therapy with canakinumab for atherosclerotic disease.N Engl J Med. 2017; 377: 1119-1131Crossref PubMed Scopus (4673) Google Scholar, 36Ismahil M.A. Hamid T. Bansal S.S. Patel B. Kingery J.R. Prabhu S.D. Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis.Circ Res. 2014; 114: 266-282Crossref PubMed Scopus (237) Google Scholar, 37Bansal S.S. Ismahil M.A. Goel M. Patel B. Hamid T. Rokosh G. Prabhu S.D. Activated T lymphocytes are essential drivers of pathological remodeling in ischemic heart failure.Circ Heart Fail. 2017; 10: e003688Crossref PubMed Scopus (154) Google Scholar, 38Bansal S.S. Ismahil M.A. Goel M. Zhou G. Rokosh G. Hamid T. Prabhu S.D. Dysfunctional and proinflammatory regulatory T-lymphocytes are essential for adverse cardiac remodeling in ischemic cardiomyopathy.Circulation. 2019; 139: 206-221Crossref PubMed Scopus (115) Google Scholar, 39Coles B. Fielding C.A. Rose-John S. Scheller J. Jones S.A. O'Donnell V.B. Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo.Am J Pathol. 2007; 171: 315-325Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 40Olsen F. Transfer of arterial hypertension by splenic cells from DOCA-salt hypertensive and renal hypertensive rats to normotensive recipients.Acta Pathol Microbiol Scand C. 1980; 88: 1-5PubMed Google Scholar, 41Guzik T.J. Hoch N.E. Brown K.A. McCann L.A. Rahman A. Dikalov S. Goronzy J. Weyand C. Harrison D.G. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction.J Exp Med. 2007; 204: 2449-2460Crossref PubMed Scopus (1300) Google Scholar, 42Mian M.O. Barhoumi T. Briet M. Paradis P. Schiffrin E.L. Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses.J Hypertens. 2016; 34: 97-108Crossref PubMed Scopus (62) Google Scholar, 43Nguyen H. Chiasson V.L. Chatterjee P. Kopriva S.E. Young K.J. Mitchell B.M. Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension.Cardiovasc Res. 2013; 97: 696-704Crossref PubMed Scopus (179) Google Scholar, 44Haudek S.B. Cheng J. Du J. Wang Y. Hermosillo-Rodriguez J. Trial J. Taffet G.E. Entman M.L. Monocytic fibroblast precursors mediate fibrosis in angiotensin-II-induced cardiac hypertrophy.J Mol Cell Cardiol. 2010; 49: 499-507Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar, 45Wang L. Zhang Y.L. Lin Q.Y. Liu Y. Guan X.M. Ma X.L. Cao H.J. Liu Y. Bai J. Xia Y.L. Du J. Li H.H. CXCL1-CXCR2 axis mediates angiotensin II-induced cardiac hypertrophy and remodelling through regulation of monocyte infiltration.Eur Heart J. 2018; 39: 1818-1831Crossref PubMed Scopus (130) Google Scholar, 46Willeford A. Suetomi T. Nickle A. Hoffman H.M. Miyamoto S. Heller Brown J. CaMKIIδ-mediated inflammatory gene expression and inflammasome activation in cardiomyocytes initiate inflammation and induce fibrosis.JCI Insight. 2018; 3: e97054Crossref PubMed Scopus (73) Google Scholar, 47Han Y.L. Li Y.L. Jia L.X. Cheng J.Z. Qi Y.F. Zhang H.J. Du J. Reciprocal interaction between macrophages and T cells stimulates IFN-gamma and MCP-1 production in Ang II-induced cardiac inflammation and fibrosis.PLoS One. 2012; 7: e35506Crossref PubMed Scopus (72) Google Scholar, 48Zhao L. Cheng G. Jin R. Afzal M.R. Samanta A. Xuan Y.T. Girgis M. Elias H.K. Zhu Y. Davani A. Yang Y. Chen X. Ye S. Wang O.L. Chen L. Hauptman J. Vincent R.J. Dawn B. Deletion of interleukin-6 attenuates pressure overload-induced left ventricular hypertrophy and dysfunction.Circ Res. 2016; 118: 1918-1929Crossref PubMed Scopus (152) Google Scholar, 49Suetomi T. Willeford A. Brand C.S. Cho Y. Ross R.S. Miyamoto S. Brown J.H. Inflammation and NLRP3 inflammasome activation initiated in response to pressure overload by Ca(2+)/calmodulin-dependent protein kinase ii delta signaling in cardiomyocytes are essential for adverse cardiac remodeling.Circulation. 2018; 138: 2530-2544Crossref PubMed Scopus (137) Google Scholar, 50Patel B. Ismahil M.A. Hamid T. Bansal S.S. Prabhu S.D. Mononuclear phagocytes are dispensable for cardiac remodeling in established pressure-overload heart failure.PLoS One. 2017; 12: e0170781Crossref PubMed Scopus (37) Google Scholar, 51Patel B. Bansal S.S. Ismahil M.A. Hamid T. Rokosh G. Mack M. Prabhu S.D. CCR2(+) monocyte-derived infiltrating macrophages are required for adverse cardiac remodeling during pressure overload.JACC Basic Transl Sci. 2018; 3: 230-244Crossref PubMed Scopus (131) Google Scholar, 52Laroumanie F. Douin-Echinard V. Pozzo J. Lairez O. Tortosa F. Vinel C. Delage C. Calise D. Dutaur M. Parini A. Pizzinat N. CD4+ T cells promote the transition from hypertrophy to heart failure during chronic pressure overload.Circulation. 2014; 129: 2111-2124Crossref PubMed Scopus (169) Google Scholar, 53Nevers T. Salvador A.M. Grodecki-Pena A. Knapp A. Velazquez F. Aronovitz M. Kapur N.K. Karas R.H. Blanton R.M. Alcaide P. Left ventricular T-cell recruitment contributes to the pathogenesis of heart failure.Circ Heart Fail. 2015; 8: 776-787Crossref PubMed Scopus (159) Google Scholar, 54Nevers T. Salvador A.M. Velazquez F. Ngwenyama N. Carrillo-Salinas F.J. Aronovitz M. Blanton R.M. Alcaide P. Th1 effector T cells selectively orchestrate cardiac fibrosis in nonischemic heart failure.J Exp Med. 2017; 214: 3311-3329Crossref PubMed Scopus (96) Google Scholar, 55Wang H. Kwak D. Fassett J. Liu X. Yao W. Weng X. Xu X. Xu Y. Bache R.J. Mueller D.L. Chen Y. Role of bone marrow-derived CD11c(+) dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.Basic Res Cardiol. 2017; 112: 25Crossref PubMed Scopus (25) Google Scholar, 56Kallikourdis M. Martini E. Carullo P. Sardi C. Roselli G. Greco C.M. Vignali D. Riva F. Ormbostad Berre A.M. Stolen T.O. Fumero A. Faggian G. Di Pasquale E. Elia L. Rumio C. Catalucci D. Papait R. Condorelli G. T cell costimulation blockade blunts pressure overload-induced heart failure.Nat Commun. 2017; 8: 14680Crossref PubMed Scopus (102) Google Scholar, 57Groschel C. Sasse A. Rohrborn C. Monecke S. Didie M. Elsner L. Kruse V. Bunt G. Lichtman A.H. Toischer K. Zimmermann W.H. Hasenfuss G. Dressel R. T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure.Sci Rep. 2017; 7: 15998Crossref PubMed Scopus (22) Google Scholar, 58Verma S.K. Garikipati V.N.S. Krishnamurthy P. Schumacher S.M. Grisanti L.A. Cimini M. Cheng Z. Khan M. Yue Y. Benedict C. Truongcao M.M. Rabinowitz J.E. Goukassian D.A. Tilley D. Koch W.J. Kishore R. Interleukin-10 inhibits bone marrow fibroblast progenitor cell-mediated cardiac fibrosis in pressure-overloaded myocardium.Circulation. 2017; 136: 940-953Crossref PubMed Scopus (49) Google Scholar, 59Altara R. Manca M. Hessel M.H. Gu Y. van Vark L.C. Akkerhuis K.M. Staessen J.A. Struijker-Boudier H.A. Booz G.W. Blankesteijn W.M. CXCL10 is a circulating inflammatory marker in patients with advanced heart failure: a pilot study.J Cardiovasc Transl Res. 2016; 9: 302-314Crossref PubMed Scopus (48) Google Scholar, 60Ngwenyama N. Salvador A.M. Velazquez F. Nevers T. Levy A. Aronovitz M.J. Luster A.D. Huggins G.S. Alcaide P. CXCR3 regulates CD4+ T cell cardiotropism in pressure overload induced cardiac dysfunction.JCI Insight. 2019; 4: 125527Crossref PubMed Scopus (35) Google Scholar, 61Salvador A.M. Nevers T. Velazquez F. Aronovitz M. Wang B. Abadia Molina A. Jaffe I.Z. Karas R.H. Blanton R.M. Alcaide P. Intercellular adhesion molecule 1 regulates left ventricular leukocyte infiltration, cardiac remodeling, and function in pressure overload-induced heart failure.J Am Heart Assoc. 2016; 5: e003126Crossref PubMed Scopus (76) Google Scholar, 62Meier L.A. Binstadt B.A. The contribution of autoantibodies to inflammatory cardiovascular pathology.Front Immunol. 2018; 9: 911Crossref PubMed Scopus (24) Google Scholar, 63Baldeviano G.C. Barin J.G. Talor M.V. Srinivasan S. Bedja D. Zheng D. Gabrielson K. Iwakura Y. Rose N.R. Cihakova D. Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy.Circ Res. 2010; 106: 1646-1655Crossref PubMed Scopus (225) Google Scholar, 64Valaperti A. Marty R.R. Kania G. Germano D. Mauermann N. Dirnhofer S. Leimenstoll B. Blyszczuk P. Dong C. Mueller C. Hunziker L. Eriksson U. CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis.J Immunol. 2008; 180: 2686-2695Crossref PubMed Scopus (123) Google Scholar, 65Tarrio M.L. Grabie N. Bu D.X. Sharpe A.H. Lichtman A.H. PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis.J Immunol. 2012; 188: 4876-4884Crossref PubMed Scopus (184) Google Scholar, 66Klee N.S. McCarthy C.G. Martinez-Quinones P. Webb R.C. Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy.Ther Adv Cardiovasc Dis. 2017; 11: 297-317Crossref PubMed Scopus (15) Google Scholar, 67Vandanmagsar B. Youm Y.H. Ravussin A. Galgani J.E. Stadler K. Mynatt R.L. Ravussin E. Stephens J.M. Dixit V.D. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.Nat Med. 2011; 17: 179-188Crossref PubMed Scopus (1805) Google Scholar, 68Abdullah C.S. Li Z. Wang X. Jin Z.Q. Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced diabetic cardiomyopathy.Int Immunopharmacol. 2016; 39: 251-264Crossref PubMed Scopus (25) Google Scholar, 69Siegismund C.S. Escher F. Lassner D. Kuhl U. Gross U. Fruhwald F. Wenzel P. Munzel T. Frey N. Linke R.P. Schultheiss H.P. Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis.Eur J Heart Fail. 2018; 20: 751-757Crossref PubMed Scopus (28) Google Scholar, 70Smorodinova N. Blaha M. Melenovsky V. Rozsivalova K. Pridal J. Durisova M. Pirk J. Kautzner J. Kucera T. Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm.PLoS One. 2017; 12: e0172691Crossref PubMed Scopus (35) Google Scholar, 71Chen M.C. Chang J.P. Liu W.H. Yang C.H. Chen Y.L. Tsai T.H. Wang Y.H. Pan K.L. Increased inflammatory cell infiltration in the atrial myocardium of patients with atrial fibrillation.Am J Cardiol. 2008; 102: 861-865Abstract Full Text Full Text P