Genetically human
apolipoprotein E (
APOE) ε32 is associated with a decreased risk of
ischemic heart disease.
ApoE deficiency in mice impairs
infarct healing after
myocardial infarction (MI). After the ischemic injury, a large number of neutrophils are firstly recruited into the
infarct zone and then degrade dead material and promote reparative phase transformation. The role of
ApoE in
inflammation response in the early stage of MI remains largely unclear. In this study, we investigated the effect of
ApoE deficiency on neutrophils' function and myocardial injury after
myocardial infarction. By left coronary artery
ligation in
ApoE -/- and wild-type (WT) mice, we observed increased
infarct size and neutrophil infiltration in
ApoE -/- mice. Within the
infarct zone, more neutrophil extracellular traps (NETs) were observed in
ApoE -/- mice, while increased ex vivo NET formation was detected in
ApoE -/- mouse-derived neutrophils through the
NADPH oxidase-ROS-dependent pathway. Suppressing overproduced NETs reduced myocardial injury in
ApoE -/- mice after
ligation. In general, our findings reveal a critical role of
apolipoprotein E in regulating Ly6G+ neutrophil activation and NET formation, resulting in limiting myocardial injury after
myocardial infarction. In such a process,
apolipoprotein E regulates NET formation via the ROS-MAPK-MSK1 pathway.