ABC | Volume 112, Nº5, May 2019

Viewpoint Souza et al. Resident macrophages and heart rate Arq Bras Cardiol. 2019; 112(5):588-591 1. Pastore CA, Pinho JA, Pinho C, Samesima N, Pereira Filho HG, Kruse JCL, et al. III Diretrizes da SociedDE bRsileira de Cardiologia sobre análise e emissão de laudos eletrocardiográficos. Arq Bras Cardiol. 2016;106(4):1–23. 2. Olshansky B. Does First Degree AV Block Have Importance in Patients Considered for Cardiac Resynchronization Therapy?: Giving It the Third Degree ∗ . JACC Clin Electrophysiol. 2017;3(8):827–9. 3. Nguyen KD, Qiu Y, Cui X, Goh YPS, Mwangi J, David T, et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature.;480(7375):104–8. 4. Theurl I, Hilgendorf I, Nairz M, Tymoszuk P, Haschka D, Asshoff M, et al. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat Med. 2016;22(8):945–51. 5. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic Pruning byMicroglia Is Necessary for Normal BrainDevelopment. Science. 2011;333(6048):1456–8. 6. Davis MJ, Tsang TM, Qiu Y, Dayrit JK, Freij JB, Huffnagle GB, et al. Macrophage M1/M2 Polarization Dynamically Adapts to Changes in CytokineMicroenvironments in Cryptococcus neoformans Infection. mBio [Internet]. [citado 20 de junho de 2018]. Disponível em: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC3684832/ 7. Pinto AR, Paolicelli R, Salimova E, Gospocic J, Slonimsky E, Bilbao-Cortes D, et al. An Abundant Tissue Macrophage Population in the Adult Murine Heart with a Distinct Alternatively-Activated Macrophage Profile. PLOS ONE. 2012;7(5):e36814. 8. Vozzi C, Dupont E, Coppen SR, Yeh HI, Severs NJ. Chamber-related differences in connexin expression in the human heart. J Mol Cell Cardiol. maio de 1999;31(5):991–1003. 9. Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, et al. Macrophages Facilitate Electrical Conduction in the Heart. Cell. 2017;169(3):510-22.e20. 10. Rosenthal N. A guardian of the heartbeat. NEngl J Med. 2017; 377(1):84–6. 11. Monnerat G, Alarcón ML, Vasconcellos LR, Hochman-Mendez C, Brasil G, Bassani RA, et al. Macrophage-dependent IL-1 β production induces cardiac arrhythmias in diabetic mice. Nat Commun. 2016;7:13344. References Thus, a possible bias is one in which macrophages contribute to the arrhythmic complications of infectious, atherosclerotic and septicemic diseases, in which their inflammatory responses may interfere with their role in modulating electrical conduction of the cardiomyocyte. 11,12,15 Research has shown that sepsis is associated with an increased risk of acute and fatal coronary disease, but its cause is still a matter of debate, and acute coronary disease prevention may be an important consideration in post-sepsis medical care. 16,17 Despite significant advances in prevention and treatment, cardiovascular diseases (CVD) continue to be the most common cause of death in the world. In fact, severe heart failure is more prevalent than cancer. 18 Several studies have demonstrated that pathological cardiac hypertrophy and fibrosis in heart failure are accompanied by a systemic inflammatory response, infiltration and activation of cells of the immune system. 19 In view of this, immunotherapies for cardiovascular diseases are on the rise. The first cardiovascular immunotherapy was developed for the treatment of hypercholesterolemia and its positive results paved the way for the clinical evaluation of anti- inflammatory immunotherapy directed to interleukin 1 β . CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that subcutaneous injections of canakinumab (ACZ885), a human monoclonal antibody that selectively neutralizes IL-1 β , significantly reduced levels of systemic inflammatory biomarkers in patients after acute myocardial infarction, reducing risk cardiovascular disease in patients with previous heart attack and inflammatory atherosclerosis. 20 Another study using CANTOS reinforces this idea and provides strong evidence that the modulation of the IL-6-induced signaling pathway induced by IL-1 α is associated with reduced rates of cardiovascular changes and mortality. 13 It is clear that further studies should be performed to address the actual involvement of resident macrophages in heart diseases. If alterations in macrophages’ function are linked to these clinical conditions, immunotherapy with macrophage reprogramming in situ could be a reliable form of therapeutic strategy that could be applied to ensure normal cardiac rhythm in patients with signs of arrhythmia. 20,21 However, what we know so far is that resident macrophages act as "masters", orchestrating the heart rate. Author contributions Conception and design of the research and Critical revision of the manuscript for intellectual content: Souza DS, Barreto TO, Cruz JS; Writing of the manuscript: Souza DS, Barreto TO, Santana MNS, Menezes-Filho JER, Cruz JS, Vasconcelos CML. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by CNPq and CAPES. Study Association This study is not associatedwith any thesis or dissertationwork. 590