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Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges

  • Amit Saxena
    Affiliations
    Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY
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  • Ilaria Russo
    Affiliations
    Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY
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  • Nikolaos G. Frangogiannis
    Correspondence
    Reprint requests: Nikolaos G. Frangogiannis, Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer G46B, Bronx, NY 10461
    Affiliations
    Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY
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      In the infarcted myocardium, necrotic cardiomyocytes release danger signals, activating an intense inflammatory response. Inflammatory pathways play a crucial role in regulation of a wide range of cellular processes involved in injury, repair, and remodeling of the infarcted heart. Proinflammatory cytokines, such as tumor necrosis factor α and interleukin 1, are markedly upregulated in the infarcted myocardium and promote adhesive interactions between endothelial cells and leukocytes by stimulating chemokine and adhesion molecule expression. Distinct pairs of chemokines and chemokine receptors are implicated in recruitment of various leukocyte subpopulations in the infarcted myocardium. For more than the past 30 years, extensive experimental work has explored the role of inflammatory signals and the contributions of leukocyte subpopulations in myocardial infarction. Robust evidence derived from experimental models of myocardial infarction has identified inflammatory targets that may attenuate cardiomyocyte injury or protect from adverse remodeling. Unfortunately, attempts to translate the promising experimental findings to clinical therapy have failed. This review article discusses the biology of the inflammatory response after myocardial infarction, attempts to identify the causes for the translational failures of the past, and proposes promising new therapeutic directions. Because of their potential involvement in injurious, reparative, and regenerative responses, inflammatory cells may hold the key for design of new therapies in myocardial infarction.

      Abbreviations:

      eRNA (extracellular RNA), HMGB1 (high mobility group box 1), HSP (heat shock protein), IL (interleukin), IL-1R1 (type 1 IL-1 receptor), IL-1Ra. (IL-1 receptor antagonist), IP (interferon-γ-inducible protein), MCP (monocyte chemoattractant protein), NSAIDs (non-steroidal anti-inflammatory drugs), RANTES (regulated on activation normal T cell expressed and secreted), SDF (stromal cell-derived factor), STEMI (ST elevation myocardial infarction), TGF (transforming growth factor), TNF (tumor necrosis factor)
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