Figure 1: Human vulnerable atherosclerotic plaques have decreased 5-LOX SPM levels and a lower SPM:LT ratio than stable lesions.

(a) Flash-frozen human plaques were separated into vulnerable (V) and stable (S) regions (left panel), which were quantified for fibrous cap thickness:lesion area ratio (top right panel) and percent plaque necrosis (bottom right panel). (t-test, **P<0.01, n=8 donors). (b) Quantification of key DHA-derived lipid mediators, with their respective biosynthetic pathways indicated (LOX, lipoxygenase). (c) Quantification of key AA-derived lipid mediators. (d) Comparison of 5-LOX-derived SPMs (RvD1 and LXA₄) and the SPM:LT ratio in vulnerable versus stable regions. For (b–d), t-test, *P<0.05, n=15 donors. (e) Quantification of RvD1 by ELISA in human macrophages that were incubated for 5 h with vehicle control, or 35 μM of 7KC, followed by Veh or 10 μM DHA, for an additional 40 min, and then the media were assayed for RvD1 with or without a 1 h pre-incubation with 10 μM NAC. Data are shown as mean±s.e.m. (n=4 separate donors). Statistical analysis was conducted using one-way ANOVA with the Kruskal–Wallis test and Dunn’s multiple comparison post-hoc analysis, *P<0.05 of n=4 separate donors. (f) Quantification nuclear:non-nuclear 5-LOX ratio by confocal microscopy in macrophages incubated as in e, with two additional groups, NAC alone and 7KC+NAC. Images were acquired on a Leica confocal microscope, and nuclear:non-nuclear 5-LOX MFI was quantified using Image J. Data are shown as mean±s.e.m. (n=4 separate donors). Statistical analysis was conducted using one-way ANOVA with the Kruskal–Wallis test with the Dunn’s multiple comparison post-hoc analysis, *P<0.05.