Excessive Neutrophil Extracellular Trap Formation Aggravates Acute Myocardial Infarction Injury in Apolipoprotein E Deficiency Mice via the ROS-Dependent Pathway

Figure 7

Schematic model of the role of ApoE/APOE3 in regulating neutrophil function, especially NET formation, in the context of acute myocardial infarction. After acute myocardial infarction, neutrophils are mainly mobilized from the bone marrow, infiltrate into the infarcted heart, and form NETs via the NADPH oxidase-ROS-MAPK-MSK1 signal pathway. In this process, apolipoprotein E regulates neutrophil infiltration and NET formation. As for NET formation, apolipoprotein E fails to reduce ROS generation but can inhibit MSK1 phosphorylation. Additionally, P38 MAPK is sensitive to apolipoprotein E deficiency. The APOE3 supplement inhibits P38 MAPK phosphorylation under the conditions of apolipoprotein E deficiency. Moreover, ApoE deficiency promotes PMA-induced ERK1/2 phosphorylation, but APOE3 fails to inhibit ERK1/2 phosphorylation after PMA treatment.