{'fraction_non_alphanumeric': 0.02527505203687184, 'fraction_numerical': 0.013083556348498365, 'mean_word_length': 6.03765690376569, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Letter by Li et al Regarding Article, "Dectin-1 Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Macrophage Polarization and Neutrophil Infiltration".

July 30, 2019 e177 Yangxin Li, PhD Zhenya Shen, MD, PhD Xi-yong Yu, MD, PhD To the Editor: We read with great interest the article by Fan et al,1 who demonstrate that Dectin-1–mediated macrophage polarization plays an important role in cardiac ischemia/reperfusion (I/R) injury. They found that Dectin-1 inhibition led to significant improvement in cardiac function, which was associated with a decrease in M1 macrophage polarization and reduced infiltration of Ly-6C+ monocyte and neutrophil. Specifically, they show that circulating Dectin-1+CD14++CD16− and Dectin1+CD14++CD16+ monocyte levels are significantly higher in patients with myocardial infarction and positively correlated with the severity of cardiac dysfunction. This excellent study supports the notion that therapeutic strategies targeting macrophage hold promise in preventing cardiac I/R injury.2,3 In light of these novel exciting developments in macrophage research, we underscore some important additional points about the development of macrophage subset–specific and stage–specific strategies to prevent/cure heart disease. One recent study showed that genetic deletion or pharmaceutical inhibition of MKL1 (megakaryocytic leukemia 1) attenuated cardiac I/R injury in mice. Their findings provide a novel link between MKL1-mediated epigenetic regulation of NADPH oxidase transcription in macrophages and reactive oxygen species accumulation in injured myocardium. Using syngeneic cardiac transplantation to model I/R injury, Bajpai et al3 demonstrated that monocyte recruitment was differentially regulated by distinct subsets of tissue-resident cardiac macrophages. They found that tissue-resident CCR2+ macrophages promoted, whereas CCR2− macrophages inhibited monocyte recruitment. They further showed that selective depletion of tissue-resident CCR2+ macrophages before myocardial infarction inhibited monocyte recruitment and improved left ventricular function. It would be interesting to find out whether Dectin-1 inhibition could decrease the expression of MKL1 and tissue-resident CCR2+ macrophages, and reduce reactive oxygen species accumulation by inhibiting NADPH oxidase transcription in macrophages. Several studies also indicate that macrophages contribute to heart development, cardiac function, and regeneration. Neonates depleted of macrophages were unable to regenerate myocardia, leading to impaired cardiac function and angiogenesis. Microarray analysis of cardiac macrophages from regenerating and nonregenerating hearts revealed that regenerative macrophages have a unique polarization phenotype and secrete numerous soluble factors that facilitate the formation of new myocardium.4 Moreover, one study discovered a subset of macrophages residing within the atrioventricular node can electrically modulate myocytes and macrophage-subset ablation induces atrioventricular block. These observations suggest that specific macrophage subsets are involved in cardiac conduction.5 Along this line, it would be interesting to find out whether inhibition of Dectin-1 would influence heart development and play a critical role in heart rhythm. © 2019 American Heart Association, Inc. LETTER TO THE EDITOR