TY - JOUR
T1 - Emerging roles of neutrophil-borne S100A8/A9 in cardiovascular inflammation
AU - Sreejit, Gopalkrishna
AU - Abdel Latif, Ahmed
AU - Murphy, Andrew J.
AU - Nagareddy, Prabhakara R.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/11
Y1 - 2020/11
N2 - Elevated neutrophil count is associated with higher risk of major adverse cardiac events including myocardial infarction and early development of heart failure. Neutrophils contribute to cardiac damage through a number of mechanisms, including attraction of other immune cells and release of inflammatory mediators. Recently, a number of independent studies have reported a causal role for neutrophil-derived alarmins (i.e. S100A8/A9) in inducing inflammation and cardiac injury following myocardial infarction (MI). Furthermore, a positive correlation between serum S100A8/A9 levels and major adverse cardiac events (MACE) in MI patients was also observed implying that targeting neutrophils or their inflammatory cargo could be beneficial in reducing heart failure. However, contradictory to this idea, neutrophils and neutrophil-derived S100A8/A9 also seem to play a vital role in the resolution of inflammation. Thus, a better understanding of how neutrophils balance these seemingly contrasting functions would allow us to develop effective therapies that preserve the inflammation-resolving function while restricting the damage caused by inflammation. In this review, we specifically discuss the mechanisms behind neutrophil-derived S100A8/A9 in promoting inflammation and resolution in the context of MI. We also provide a perspective on how neutrophils could be potentially targeted to ameliorate cardiac inflammation and the ensuing damage.
AB - Elevated neutrophil count is associated with higher risk of major adverse cardiac events including myocardial infarction and early development of heart failure. Neutrophils contribute to cardiac damage through a number of mechanisms, including attraction of other immune cells and release of inflammatory mediators. Recently, a number of independent studies have reported a causal role for neutrophil-derived alarmins (i.e. S100A8/A9) in inducing inflammation and cardiac injury following myocardial infarction (MI). Furthermore, a positive correlation between serum S100A8/A9 levels and major adverse cardiac events (MACE) in MI patients was also observed implying that targeting neutrophils or their inflammatory cargo could be beneficial in reducing heart failure. However, contradictory to this idea, neutrophils and neutrophil-derived S100A8/A9 also seem to play a vital role in the resolution of inflammation. Thus, a better understanding of how neutrophils balance these seemingly contrasting functions would allow us to develop effective therapies that preserve the inflammation-resolving function while restricting the damage caused by inflammation. In this review, we specifically discuss the mechanisms behind neutrophil-derived S100A8/A9 in promoting inflammation and resolution in the context of MI. We also provide a perspective on how neutrophils could be potentially targeted to ameliorate cardiac inflammation and the ensuing damage.
KW - Cardiac Inflammation
KW - DAMPs
KW - Myocardial Infarction
KW - Neutrophils
KW - S100A8/A9
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U2 - 10.1016/j.phrs.2020.105212
DO - 10.1016/j.phrs.2020.105212
M3 - Review article
C2 - 32991974
AN - SCOPUS:85092101390
SN - 1043-6618
VL - 161
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 105212
ER -