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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: July 17, 2015
Accepted:
July 9,
2015
Received in revised form:
July 8,
2015
Received:
April 2,
2015
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
