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

Figure 5

APOE3 affects NET formation through the MAPK-MSK1 pathway. (a) Quantitation of ex vivo NET formation of WT- and ApoE^-/--derived neutrophils stimulated with PMA and different concentrations of the P38 MAPK inhibitor (SB239063 or losmapimod) or the ERK inhibitor (FR180204) for 4 hours. (b, c) Western blots and quantitation of the ERK1/2 (ERK), phosphorylated ERK1/2 (p-ERK), JNK, phosphorylated JNK (p-JNK), P38 MAPK, and phosphorylated P38 MAPK (p-P38 MAPK) expressions in WT- and ApoE^-/--derived neutrophils stimulated with PBS, PMA, or PMA plus APOE3 for 1 hour. (d, e) Western blots and quantitation of the phosphorylated MSK1 (p-MSK1) and the phosphorylated ATF2 (p-ATF2) expression in WT- and ApoE^-/--derived neutrophils stimulated with PBS, PMA, or PMA plus APOE3 for 1 hour. Columns filled with black: WT mouse-derived neutrophils. Columns filled with white: ApoE^-/- mouse-derived neutrophils. Data are shown as . Statistical tests include the one-way analysis of variance followed by Dunnett’s multiple comparison test (a) and the Kruskal-Wallis test followed by Dunn’s multiple comparison test (c, e). and .

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