TY - JOUR
T1 - Inflammation as a therapeutic target in myocardial infarction
T2 - Learning from past failures to meet future challenges
AU - Saxena, Amit
AU - Russo, Ilaria
AU - Frangogiannis, Nikolaos G.
N1 - Funding Information:
Conflicts of Interest: All authors have read the journal’s policy on disclosure of potential conflicts of interest and have none to declare. Dr Frangogiannis' laboratory is supported by the National Institutes of Health grants R01 HL76246 and R01 HL85440 . Ilaria Russo is supported by training grants from the Fondazione Cassa di Risparmio di Lucca and the Fondazione Banca del Monte di Lucca . All authors have reviewed and approved the manuscript and have read the journal's authorship agreement.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.trsl.2015.07.002
DO - 10.1016/j.trsl.2015.07.002
M3 - Review article
C2 - 26241027
AN - SCOPUS:84952639700
SN - 1931-5244
VL - 167
SP - 152
EP - 166
JO - Translational Research
JF - Translational Research
IS - 1
ER -
